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WO2019035068A1 - Mesure non invasive d'antibiotiques du type rifamicyne - Google Patents

Mesure non invasive d'antibiotiques du type rifamicyne Download PDF

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Publication number
WO2019035068A1
WO2019035068A1 PCT/IB2018/056213 IB2018056213W WO2019035068A1 WO 2019035068 A1 WO2019035068 A1 WO 2019035068A1 IB 2018056213 W IB2018056213 W IB 2018056213W WO 2019035068 A1 WO2019035068 A1 WO 2019035068A1
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WIPO (PCT)
Prior art keywords
spectrum
patient
antibiotic drug
measured
rifamycin antibiotic
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Ceased
Application number
PCT/IB2018/056213
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English (en)
Inventor
Andreas DIACON
Thomas Richard NIESLER
Solomon Petrus LE ROUX
Veronique Rejean DE JAGER
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Task Research Centre
Stellenbosch University
Original Assignee
Task Research Centre
Stellenbosch University
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Publication date
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Publication of WO2019035068A1 publication Critical patent/WO2019035068A1/fr
Anticipated expiration legal-status Critical
Priority to ZA2020/01205A priority Critical patent/ZA202001205B/en
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
    • A61B5/4839—Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4848—Monitoring or testing the effects of treatment, e.g. of medication
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6814—Head
    • A61B5/6815—Ear
    • A61B5/6816—Ear lobe
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6825—Hand
    • A61B5/6826—Finger

Definitions

  • This invention relates to a non-invasive and real-time method of measuring a rifamycin antibiotic drug in a patient.
  • it relates to the measurement of a level of a rifamycin antibiotic drug, such as rifampicin and rifapentine, in tissue and the bloodstream of a patient.
  • the rifamycins are a class of antibiotics which includes the therapeutically useful derivatives rifampicin, rifabutin, rifapentine, rifalazil and rifaximin. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective against mycobacteria, and are therefore used to treat tuberculosis (TB), leprosy and mycobacterium avium complex (MAC) infections. Rifamycins have been used for the treatment of many diseases, most commonly for HIV-related TB. Rifampicin and rifapentine, in particular, find use in the treatment of TB, often in association with other agents which overcome resistance.
  • TB tuberculosis
  • MAC mycobacterium avium complex
  • Rifampicin has been used in the treatment of TB for many decades, whilst rifapentine has found more recent use in treating TB.
  • the concentration of rifampicin or rifapentine reached in human tissue and blood is critical to the success of treatment.
  • Recent evidence suggests that higher than standard doses of rifampicin may be more effective in the treatment of TB and have the potential to allow for treatment-shortening.
  • the same dosage of the drug does not produce the same tissue and/or blood concentration in all individuals, exposing those with higher concentrations to toxicity and those with lower concentrations to reduced treatment efficacy.
  • a non-invasive method of measuring a level of a rifamycin antibiotic drug in a patient using spectrophotometry comprising:
  • determining the level of the rifamycin antibiotic drug in the patient based on a comparison of the measured spectrum with a reference spectrum.
  • a further feature provides for the reference spectrum to be a spectrum measured from the same patient.
  • step of determining the level of the rifamycin antibiotic drug in the patient to include measuring a spectrum before and after administration of the rifamycin antibiotic drug and comparing the measured spectra to determine the level of the rifamycin antibiotic drug in the patient from changes in the spectrum attributable to the rifamycin antibiotic drug; and for the changes in the spectrum attributable to the rifamycin antibiotic drug to be different intensities of transmitted or reflected light within the wavelength range of 185 nm to about 1 100 nm, preferably between about 200 nm and about 700 nm, more preferably between about 420 nm and about 580 nm.
  • step of determining the level of the rifamycin antibiotic drug in the patient to include correlating the measured spectrum with measured spectra at known blood concentrations to determine the level of rifamycin antibiotic drug in the patient.
  • the measured spectrum of transmitted or reflected light to be the intensity of transmitted or reflected light within the wavelength range of about 185 nm to about 1 100 nm, preferably between about 200 nm and about 700 nm, more preferably between about 420 nm and 580 nm; and for the spectrum of transmitted or reflected light to be measured transcutaneously by placing a receiver of a light detector on a surface of the skin of the body part.
  • the body part to be an appendage; for the appendage to be well- perfused; and for the appendage to be a finger or an earlobe.
  • Still further features provide for the rifamycin antibiotic drug to be rifampicin or rifapentine; and for the patient to suffer from tuberculosis (TB).
  • a system for measuring a level of a rifamycin antibiotic drug in a patient including a memory for storing computer-readable program code and a processor for executing the computer-readable program code, the system comprising:
  • a receiving component for receiving a measured spectrum of transmitted or reflected light obtained by directing light of known spectral characteristics at a body part
  • a determining component for determining the level of the rifamycin antibiotic drug in the patient based on a comparison of the measured spectrum with a reference spectrum.
  • the system to include a comparing component for comparing spectra measured before and after administration of the rifamycin antibiotic drug to determine a level of the rifamycin antibiotic drug in the patient from changes in the spectrum attributable to the rifamycin antibiotic drug; or for the system to include a correlating component for correlating the measured spectrum with measured spectra at known blood concentrations to determine a level of rifamycin antibiotic drug in the patient.
  • a computer program product for measuring a level of a rifamycin antibiotic drug in a patient
  • the computer program product comprising a computer-readable medium having stored computer-readable program code for performing the steps of:
  • determining the level of the rifamycin antibiotic drug in the patient based on a comparison of the measured spectrum with a reference spectrum.
  • a portable device for noninvasive ⁇ measuring a level of a rifamycin antibiotic drug in a patient comprising a light source for directing light of known spectral characteristics at a body part; a spectrophotometer for measuring a spectrum or reflected or transmitted light; and a processing module configured to receive the measured spectrum and process the spectrum to determine the level of the rifamycin antibiotic drug in the patient based on a comparison of the measured spectrum with a reference spectrum.
  • the spectrophotometer to include or be connected to a light detector receiver that is configured to be placed on the skin of the body part for transcutaneous transmittance or reflectance spectral measurements; for a software application to be resident on the processing module and executable by the processing module to instruct the spectrophotometer to measure a spectrum of transmitted or reflected light over a preselected wavelength range, to receive the measured spectrum and to compare the measured spectrum to a reference spectrum to determine the level of the rifamycin antibiotic drug in the patient; for the processing module to have a memory or database associated with each patient that stores measured spectra for comparing spectra measured from the same patient.
  • Figure 1 is as schematic illustration of an embodiment of a portable device for noninvasive ⁇ measuring a level of a rifamycin antibiotic drug in a patient;
  • Figure 2 is a flow diagram that illustrates a method for non-invasively measuring a level of a rifamycin antibiotic drug in a patient
  • Figure 3 is a graph showing absorbance measurements of two different rifampicin concentrations
  • Figure 4 is a graph showing absorbance measurements of three different rifampicin concentrations and three different rifapentine concentrations
  • Figure 5 is a graph showing a measured light spectrum at various time points in an individual not exposed to rifampicin
  • Figure 6 is a graph showing a measured light spectrum for an individual exposed to rifampicin
  • Figure 7 is a graph showing a measured light spectrum for a second individual exposed to rifampicin
  • Figure 8 is a graph showing the measured light spectrum from Figure 5 in greater detail
  • Figure 9 is a graph showing the scaled measurements at 490 nm for an individual exposed to rifampicin over an extended period of time;
  • Figure 10 is a schematic illustration of a rifamycin antibiotic drug measuring system;
  • Figure 1 1 is a schematic illustration of an example of a computing device in which various aspects of the disclosure may be implemented.
  • a non-invasive method of measuring the presence or a level of a rifamycin antibiotic drug in a patient transcutaneously, i.e. through the skin, is provided and is based on the use of spectrophotometry. This method exploits the rifamycins' unique light absorbance characteristics and bright orange-red colour in blood.
  • the rifamycin class of antibiotics are characterised by a natural ansa structure. More importantly, the rifamycins include a chromophoric naphthohydroquinone group spanned by a long aliphatic bridge. As a result, they have a characteristic absorption spectrum and colour in solution.
  • the rifamycins have the following general structure:
  • R groups, Ri and R 2 in the general structure of rifamycins may vary. It is foreseen that new derivatives may be developed in future.
  • Spectrophotometry is a method of measuring the amount of light (light intensity), at different wavelengths in the electromagnetic spectrum that is absorbed, transmitted or reflected by a substance. Spectrophotometry is a quantitative method of analysis and can be used to quantify the amount of a substance in a sample. For example, the concentration of a compound in solution can be determined by spectrophotometry. In a typical laboratory setting, a calibrated light source steadily illuminates a sample placed in a cuvette. The amount of light absorbed by the substance at specific wavelengths is proportional to the concentration of the substance.
  • This change in light is measured by the spectrophotometer which accordingly yields different measured spectra for different concentrations of the same substance.
  • the concentration of a substance in solution by analysing the amount of light it absorbs or reflects.
  • the portable device (100) includes a light source (103) for directing light of known spectral characteristics at a body part (105), a spectrophotometer (107) for measuring a spectrum or reflected or transmitted light and a processing module (109) configured to receive the measured spectrum and process the spectrum to determine the level of the rifamycin antibiotic drug in a patient based on a comparison of the measured spectrum with a reference spectrum.
  • the spectrophotometer (107) includes or is connected to a light detector receiver (109) that is adapted to take transcutaneous transmittance or reflectance spectral measurements.
  • the light detector receiver (109) is configured and shaped to be placed against the skin of a patient.
  • a fibre optic probe or photodiode may include both the light source (103) and the light detector receiver (109) and these may be arranged to ensure detection of the light reflected from the body part.
  • a software application may be resident on the processing module (109) and executable by the processing module (109) to instruct the spectrophotometer to measure a spectrum of transmitted or reflected light over a preselected wavelength range, to receive or record the measured spectrum and to compare or correlate the measured spectrum to a reference spectrum to determine the presence or a level of a rifamycin antibiotic drug in a patient.
  • the processing module (109) may have a memory or database (1 1 1 ) associated with each patient that stores measured spectra from the same patient in order to allow for the comparison or correlation of spectra measured at different times in a treatment period or of prior treatments.
  • the memory may also store a baseline reference spectrum that may be simulated and/or based on spectral measurements from various patients which may serve as a control or threshold for detecting the presence of a rifamycin antibiotic drug in a patient.
  • the reference spectrum stored on the memory or in the database may also be derived from spectra measured at known blood concentrations of the rifamycin antibiotic drug, in which case a correlation of the measured spectrum with such reference spectra can be used to determine a level of the rifamycin antibiotic drug in the patient.
  • a non-invasive method of measuring a level of a rifamycin antibiotic drug in a patient using spectrophotometry is illustrated by way of the flow diagram shown in Figure 2.
  • the method includes directing light of known spectral characteristics at a body part (203) and measuring a spectrum of transmitted or reflected light (205).
  • the measured spectrum is used for determining the level of the rifamycin antibiotic drug in the patient (207) based on a comparison of the measured spectrum with a reference spectrum.
  • the reference spectrum may be a spectrum measured from the same patient. Alternatively, it may be a baseline or level-indicating spectrum derived from spectral measurements carried out on other patients that have been processed to exclude variable components or spectral characteristics encountered in different patients.
  • the step of determining the level of the rifamycin antibiotic drug in the patient may involve measuring a spectrum before and after administration of the rifamycin antibiotic drug and comparing the measured spectra (209) to determine a level of the rifamycin antibiotic drug in the patient from changes in the spectrum attributable to the rifamycin antibiotic drug.
  • the changes in the spectrum attributable to the rifamycin antibiotic drug are the different intensities of transmitted or reflected light within the wavelength range of 185 nm to about 1 100 nm, preferably between about 200 nm and about 700 nm, more preferably between about 420 nm and about 580 nm.
  • the step of determining the level of the rifamycin antibiotic drug in the patient may involve correlating the measured spectrum with measured spectra at known blood concentrations (21 1 ) to determine a level of rifamycin antibiotic drug in the patient.
  • light with known spectral characteristics is directed at a body part.
  • the light has a known intensity and known wavelength range.
  • Any suitable light source and monochromator may be used to generate polychromatic light of a selected wavelength range.
  • the strength or intensity of the light source may be selected depending on the body part on which measurements are taken, whether transmittance or reflectance spectra are measured and/or to shorten or otherwise optimise measurement times.
  • the body part that is irradiated is preferably a well-perfused appendage.
  • a well-perfused appendage is an appendage with a more than sufficient blood supply to the tissue in the appendage such as a finger or an earlobe. In a well-perfused appendage blood flows from an artery through the vascular bed of the tissue.
  • Other non-invasive locations on the body where blood flows or accumulates, such as at or near arteries under the arm may also be used.
  • a spectrum of transmitted or reflected light may be measured by placing a receiver of a light detector on the surface of the skin of the body part for transcutaneous measurements.
  • a spectrum of reflected light may be measured with the light source and the receiver of the light detector placed together on the same side or at the same location on the body part or appendage, as would be done with a fibre-optic probe or a photodiode.
  • the receiver of the detector will be arranged to be opposite the light source with the appendage between the receiver and the light source.
  • Transcutaneous spectroscopic measurements may be obtained from individuals at the same location both before and during their treatment with rifamycin-based anti-TB therapy.
  • the spectrum of either transmitted or reflected light is measured with a spectrophotometer and the spectrum is recorded and analysed.
  • the change in the chemical composition of the blood and perfused tissues when it contains a rifamycin antibiotic drug will influence characteristics of the transmitted or reflected light.
  • the intensity of transmitted or reflected light at specific wavelengths will vary depending on the concentration of the chromophoric rifamycin antibiotic drug in the tissue and blood.
  • the amount of absorption of light by rifamycin is proportional to the amount of the rifamycin antibiotic drug in the patient based on the Beer-Lambert Law which allows for the assigning of a level of the rifamycin antibiotic drug in the patient.
  • a level or approximate concentration of the rifamycin antibiotic drug in the patient, in particular in the tissue and blood of the appendage can be determined by comparing the spectrum measured before the administration of the rifamycin antibiotic drug with that measured after administration of the drug or to another reference spectrum. The difference in the intensities of transmitted or reflected light over a selected wavelength range are indicative of the relative amount or level of the rifamycin antibiotic drug in the patient.
  • the transcutaneous spectroscopic measurements may be correlated with measured spectra at known blood concentrations of the rifamycin antibiotic drug.
  • the correlation may take into account a time lag between blood concentration and the concentration of the drug in the blood and tissue of the appendage.
  • the correlation may serve as a control or may be used to optimise the method and calibrate the device employed to measure a level of a rifamycin antibiotic drug in a patient.
  • the correlation is preferably patient specific as each individual differs in the pigments and other chromophores present in their bodies.
  • Spectral measurements may be carried out at specific times over an entire treatment period to monitor the level of the rifamycin antibiotic drug in a patient. Spectral measurements may also be taken at selected times after administration so as to determine the time at which peak levels are observed in the tissue and blood and to measure the peak level or concentration of the rifamycin antiobiotic drug in the tissue and blood of the patient.
  • the intensity of transmitted or reflected light within the wavelength range of from about 185 nm to about 1 100 nm, preferably between about 200 nm and about 700 nm, may be measured. It has been observed that the greatest changes in absorbance in the measured spectra that are generally attributable to the rifamycin antibiotic drug are evident in the wavelength range of about 420 nm to about 580 nm. Accordingly, this is also the part of the spectrum that may be compared to a reference spectrum.
  • the effects of other chromophoric molecules present in the appendage may be taken into account when comparing and processing the measured difference in transmittance or absorbance of light at selected wavelengths or within selected wavelength ranges to determine the absorbance of photons that is attributable to the rifamycin antibiotic drug only.
  • the comparison of spectra may be over a wavelength range or at two or more specific wavelengths in the spectrum.
  • the difference in the intensities or transmitted or reflected light over the range or at the two or more specific wavelength can be analysed and processed to eliminate any of the known contributions of other chromophores in a patient over this wavelength range or at the specific wavelengths to determine a contribution made by a rifamycin antibiotic drug only and assign a level or rifamycin antibiotic in the patient based on the relative amount of light absorbed by the rifamycin antibiotic.
  • the comparison of absorbance at different wavelengths in the same spectrum is useful to identify and disregard the light absorbance of other chromophores present in the patient.
  • the information obtained in terms of the method can be used to detect rifamycin presence in a patient.
  • the measured spectrum may be compared and correlated with spectra measured for other patients that have not ingested or otherwise been exposed to the rifamycin antibiotic drug to determine a threshold or baseline measurement.
  • the information obtained in terms of the method can also be used to deduce the rifamycin level, or approximate concentration, in real-time at the bedside and without taking blood or tissue samples.
  • the ability to determine rifamycin levels in real-time will enable health professionals to immediately adjust the dose to that required to improve patient outcomes.
  • the method may find particular use in treating patients suffering from TB by monitoring the level or concentration of rifampicin or rifapentine drug in tissue and blood non-invasively and adjusting the dose to improve treatment efficacy. The method is completely pain-free.
  • the method of measuring the level or concentration of a rifamycin antibiotic such as rifampicin or rifapentine in an individual as described herein is non-invasive, pain-free and produces real-time results for immediate action.
  • the device used is portable and can thus be used at the point-of- care.
  • a number of measurements can also be recorded to describe in detail changes in rifampicin or rifapentine levels over various periods of time, as required.
  • Rifampicin and rifapentine are used for demonstration purposes because these agents are the most frequently used in treatment.
  • the rifamycin class of antibiotics display the same light absorbance properties due to their structural similarity so that the method can be applied to chemical entities of the rifamycin class in general.
  • measurements may be taken over a continuous wavelength range or at one or more discrete wavelengths to measure a rifamycin antibiotic drug in patient.
  • Any suitable instrumentation may be used to carry out the method of measuring a rifamycin antibiotic drug in a patient.
  • any suitable light source of an appropriate intensity for either reflectance or transmittance spectral measurements, for a specific location on the body from which transcutaneous and non-invasive measurements are taken, or to optimise the measurement times may be used.
  • Commonly used light sources include tungsten lamps, deuterium tungsten lamps, xenon lamps or LEDs.
  • Any suitable detector-receiver may be used in association with the spectrometer, such as a fibre-optic probe, a photodiode or the like. Examples
  • Figure 3 shows the absorbance measurements for two rifampicin concentrations which are in the range of those expected in blood using the Ocean Optics Flame-S spectrometer.
  • the samples were placed in cuvettes and the light absorbed by each sample were measured.
  • the four absorbance maxima are easily identifiable.
  • the first peak (from the left) is wider and represents two superimposed maxima.
  • Figure 4 shows the absorbance measurements of three different concentrations of both rifampicin and rifapentine, measured in the same manner. It is evident that the two different antibiotics belonging to the rifamycin group display the same absorbance characteristics by having overlapping absorption maxima. This suggests that the same non-invasive measurement procedure should suffice for these and other rifamycin antibiotics.
  • Reflectance measurements were carried out using an optical fibre reflection probe connected to a light source and the miniature Ocean Optics Flame-S spectrometer.
  • the spectrometer was connected to a processing module with suitable software thereon to receive the measured spectra.
  • light travels through the periphery of a fibre and falls on a sample placed at the tip of the probe.
  • the sample absorbs some of the light and reflects the remaining light towards a single fibre core at the centre of the probe. This reflected light is subsequently measured by the spectrometer.
  • the latter or a similar reflectance measurement technique is most appropriate to be used on patients at this time, as it allows the probe to be placed on or pressed lightly against a finger, earlobe or other skin surface without causing any pain or discomfort.
  • Figure 5 shows the natural variation of repeated measurements of an individual not exposed to rifampicin. The measurements remain fairly constant throughout the spectrum, with some variation in the spectra evident around 400 nm. This variation is expected and due to the different pigments and biochemical substances in the blood such as haemoglobin, bilirubin, and others.
  • Figure 6 shows an observable difference in the measured light spectrum before and after rifampicin intake at a dose of 10mg/kg.
  • B1 .2 refers to the time rifampicin was ingested and thus serves as a baseline measurement.
  • R1 .2 through to R8.2 indicate half hourly measurements taken chronologically after ingestion of rifampicin.
  • a lower intensity means more light was absorbed by the subcutaneous tissues and blood and therefore less was reflected. It is expected that the measurements show a lower intensity for higher concentrations of rifampicin and vice versa.
  • R2.2 to R8.2 measured from 1 hour to 4 hours after ingestion of rifampicin shows greater absorption (lower intensity reflection) at certain wavelengths than B1 .2 measured immediately after rifampicin ingestion.
  • Figure 7 shows an observable difference in the measured light spectrum before and after rifampicin ingestion in a different individual given 600 mg of rifampicin (a dose of 10 mg/kg).
  • V1 .1 is the baseline measurement
  • V1 .2 to V1 .4 reflect measurements at hourly intervals after rifampicin ingestion. Decreased intensity, and thus increased absorption, can be noted around 500 nm from V1 .1 (before rifampicin) and after rifampicin (V1 .2 to V1 .4).
  • Figure 8 shows the same measurements of Figure 7 in greater detail around 470 nm.
  • a rifamycin antibiotic drug measuring system (1000) is illustrated in Figure 10.
  • This computer system for measuring a level of a rifamycin antibiotic drug in a patient may include a processor (1002) for executing the functions of components described below, which may be provided by hardware or by software units executing on the rifamycin antibiotic drug measuring system.
  • the software units may be stored in a memory component (1004) and instructions may be provided to the processor (1002) to carry out the functionality of the described components.
  • the rifamycin antibiotic drug measuring system (1000) may include a receiving component (1006) arranged to receive a measured spectrum of transmitted or reflected light obtained by directing light of known spectral characteristics at a body part.
  • a determining component (1008) may be included and arranged to determine the level of the rifamycin antibiotic drug in the patient based on a comparison of the measured spectrum with a reference spectrum.
  • a patient measured spectra access component (1014) arranged to provide access to a database (1016) storing previously measured spectra for a specific patient as reference spectra may be included.
  • a threshold information access component (1018) may be included in the system that is arranged to provide access to the database (1016) which may also be storing a threshold or baseline spectrum.
  • the threshold or baseline spectrum may be used as reference spectrum to determine the presence or a level of a rifamycin antibiotic drug in a patient.
  • the system may further include a comparing component (1010) arranged to compare a measured spectrum to a stored spectrum from the database (1016) as may be required to compare spectra measured before and after administration of the rifamycin antibiotic drug to determine a level of the rifamycin antibiotic drug in the patient from changes in the spectrum attributable to the rifamycin antibiotic drug.
  • the system may include a correlating component (1012) arranged to correlate a measured spectrum with previously measured spectra at known blood concentrations, which may be stored in the database (1016) to determine a level of rifamycin antibiotic drug in the patient.
  • An output component (1020) arranged to provide an output of a level of a rifamycin antibiotic drug in a patient following a comparison or correlation may be included in the system to provide results to a user of the system.
  • FIG. 1 1 illustrates an example of a computing device (1 100) in which various aspects of the disclosure may be implemented.
  • the computing device (1 100) may be embodied as any form of data processing device including a personal computing device (e.g. laptop or desktop computer), a server computer (which may be self-contained, physically distributed over a number of locations), a client computer, or a communication device, such as a mobile phone (e.g. cellular telephone), satellite phone, tablet computer, personal digital assistant or the like.
  • a mobile phone e.g. cellular telephone
  • satellite phone e.g. cellular telephone
  • tablet computer e.g. cellular telephone
  • personal digital assistant e.g. cellular telephone
  • the computing device (1 100) may be suitable for storing and executing computer program code.
  • the various participants and elements in the previously described system diagrams may use any suitable number of subsystems or components of the computing device (1 100) to facilitate the functions described herein.
  • the computing device (1 100) may include subsystems or components interconnected via a communication infrastructure (1 105) (for example, a communications bus, a network, etc.).
  • the computing device (1 100) may include one or more processors (1 1 10) and at least one memory component in the form of computer-readable media.
  • the one or more processors (1 1 10) may include one or more of: CPUs, graphical processing units (GPUs), microprocessors, field programmable gate arrays (FPGAs), application specific integrated circuits (ASICs) and the like.
  • a number of processors may be provided and may be arranged to carry out calculations simultaneously.
  • various subsystems or components of the computing device (1 100) may be distributed over a number of physical locations (e.g. in a distributed, cluster or cloud-based computing configuration) and appropriate software units may be arranged to manage and/or process data on behalf of remote devices.
  • the memory components may include system memory (1 1 15), which may include read only memory (ROM) and random access memory (RAM).
  • ROM read only memory
  • RAM random access memory
  • BIOS basic input/output system
  • System software may be stored in the system memory (1 1 15) including operating system software.
  • the memory components may also include secondary memory (1 120).
  • the secondary memory (1 120) may include a fixed disk (1 121 ), such as a hard disk drive, and, optionally, one or more storage interfaces (1 122) for interfacing with storage components (1 123), such as removable storage components (e.g. magnetic tape, optical disk, flash memory drive, external hard drive, removable memory chip, etc.), network attached storage components (e.g. NAS drives), remote storage components (e.g. cloud-based storage) or the like.
  • storage components e.g. magnetic tape, optical disk, flash memory drive, external hard drive, removable memory chip, etc.
  • network attached storage components e.g. NAS drives
  • remote storage components e.g. cloud-based storage
  • the computing device (1 100) may include an external communications interface (1 130) for operation of the computing device (1 100) in a networked environment enabling transfer of data between multiple computing devices (1 100) and/or the Internet.
  • Data transferred via the external communications interface (1 130) may be in the form of signals, which may be electronic, electromagnetic, optical, radio, or other types of signal.
  • the external communications interface (1 130) may enable communication of data between the computing device (1 100) and other computing devices including servers and external storage facilities. Web services may be accessible by and/or from the computing device (1 100) via the communications interface (1 130).
  • the external communications interface (1 130) may be configured for connection to wireless communication channels (e.g., a cellular telephone network, wireless local area network (e.g.
  • the computer-readable media in the form of the various memory components may provide storage of computer-executable instructions, data structures, program modules, software units and other data.
  • a computer program product may be provided by a computer-readable medium having stored computer-readable program code executable by the central processor (1 1 10).
  • a computer program product may be provided by a non-transient computer-readable medium, or may be provided via a signal or other transient means via the communications interface (1 130).
  • Interconnection via the communication infrastructure (1 105) allows the one or more processors (1 1 10) to communicate with each subsystem or component and to control the execution of instructions from the memory components, as well as the exchange of information between subsystems or components.
  • Peripherals such as printers, scanners, cameras, or the like
  • input/output (I/O) devices such as a mouse, touchpad, keyboard, microphone, touch-sensitive display, input buttons, speakers and the like
  • I/O input/output
  • One or more displays (1 145) (which may be touch-sensitive displays) may be coupled to or integrally formed with the computing device (1 100) via a display (1 145) or video adapter (1 140).
  • a software unit is implemented with a computer program product comprising a non-transient computer-readable medium containing computer program code, which can be executed by a processor for performing any or all of the steps, operations, or processes described.
  • Software units or functions described in this application may be implemented as computer program code using any suitable computer language such as, for example, JavaTM, C++, or PerlTM using, for example, conventional or object-oriented techniques.
  • the computer program code may be stored as a series of instructions, or commands on a non-transitory computer-readable medium, such as a random access memory (RAM), a read-only memory (ROM), a magnetic medium such as a hard-drive, or an optical medium such as a CD-ROM. Any such computer-readable medium may also reside on or within a single computational apparatus, and may be present on or within different computational apparatuses within a system or network.

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  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

L'invention concerne un procédé non invasif de mesure par spectrophotométrie, sur un patient, d'un médicament antibiotique du type rifamycine. Le procédé consiste à diriger la lumière présentant des caractéristiques spectrales connues au niveau d'une partie corporelle telle qu'un appendice bien perfusé et à mesurer le spectre de lumière transmise ou réfléchie. Le procédé permet la mesure transcutanée et la détermination ultérieure d'un taux du médicament antibiotique du type rifamycine chez un patient en comparant un spectre mesuré avec un spectre de référence. L'invention concerne également un système, un produit programme d'ordinateur et un dispositif portable permettant de mettre en oeuvre le procédé de mesure non invasive d'un médicament antibiotique du type rifamycine chez un patient.
PCT/IB2018/056213 2017-08-18 2018-08-17 Mesure non invasive d'antibiotiques du type rifamicyne Ceased WO2019035068A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
ZA2020/01205A ZA202001205B (en) 2017-08-18 2020-02-26 Non-invasive measurement of rifamycin antibiotics

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ZA201705608 2017-08-18
ZA2017/05608 2017-08-18

Publications (1)

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WO2019035068A1 true WO2019035068A1 (fr) 2019-02-21

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PCT/IB2018/056213 Ceased WO2019035068A1 (fr) 2017-08-18 2018-08-17 Mesure non invasive d'antibiotiques du type rifamicyne

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WO (1) WO2019035068A1 (fr)
ZA (1) ZA202001205B (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120196887A1 (en) * 2011-02-02 2012-08-02 Darkoh Charles Methods and compositions for improved rifamycin therapies

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120196887A1 (en) * 2011-02-02 2012-08-02 Darkoh Charles Methods and compositions for improved rifamycin therapies

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
FERREIRA D A ET AL: "ANALYSIS OF THE MOLECULAR ASSOCIATION OF RIFAMPICIN WITH HYDROXYPROPYL-BETA-CYCLODEXTRIN", REVISTA BRASILEIRA DE CIENCIAS FARMACEUTICAS - BRAZILIAN JOURNALOF PHARMACEUTICAL SCIE, FACULDADE DE CIENCIAS FARMACEUTICAS, SAO PAULO, BR, vol. 40, no. 1, 1 January 2004 (2004-01-01), pages 43 - 51, XP009044012, ISSN: 1516-9332 *
RAJARAM SUBASHINI ET AL: "Ascorbic acid improves stability and pharmacokinetics of rifampicin in the presence of isoniazid", JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, NEW YORK, NY, US, vol. 100, 1 August 2014 (2014-08-01), pages 103 - 108, XP029067070, ISSN: 0731-7085, DOI: 10.1016/J.JPBA.2014.07.027 *

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