Rifampicin

The poorly water soluble anti tubercular drug namely Rifampicin was selected for the study and were used to prepare inclusion complexes with βCD and HPβCD by three methods viz. coevaporation, kneading and physical mixing method, in each case 1:1 and 1:2M (drug: cyclodextrins) ratios were prepared.The phase solubility study results reveals the solubilizing efficiency of CDs is in the order of HPβCD > βCD. The dissolution studies of the inclusion complexes without the polymer in kneading method were found to be greater than the other methods i.e. physical and co-precipitation method. The dissolution studies of inclusion complexes of 1:2 kneading method was optimized and the polymers (PVP and HPMC) were added in different concentrations of 1:2:0.1,1:2:0.2 and 1:2:0.3.out of which the higher concentration of polymer was found to release more percent of Rifampicin. The present work was fulfilled by the preparation of fast dissolving tablets with inclusion complex constituting drug, HPβCD and PVP in the ratio 1:2:0.3 and super disintegrant(Cross caramellose sodium).The bioavailability of Rifampicin was increased by 4 folds as compared to the pure drug by formulating it as a fast dissolving tablet with an inclusion complex.

Thrombocytopenia is an uncommon but potentially life threatening complication of certain anti-tubercular drugs and is characterized by rapid destruction of platelets whenever an offending drug is taken by a susceptible person. Here is a case report of Rifampicin induced Thrombocytopenia. This case is being reported for purpose of its rare occurrence and documentation.

Rifampicin is an antibiotic of the group of naphtalenics ansamicins, produced by Streptomyves mediterranei. This drug was discovered in the 60's, with bactericidal activity about 95% of sensitive strains of Mycobacterium tuberculosis and Mycobacterium leprae, the etiologic agents of tuberculosis and leprosy, respectively. Investigations have shown that the main limitation of some formulations of rifampicin is due to their low solubility in aqueous medium, which fits in class II Biopharmaceutical Classification System. Objective: In this regard, the objective of this review was to demonstrate the main techniques used to optimize the dissolution profile of the drug rifampin. Methods: The scientific review was developed by database search Pub Med, Science direct, Scopus, CAPES Periodicals and ACS Publications, using the keywords rifampicin, release system, dissolution and their associations in the period March to June 2014 in documents published in the year 1971 to 2013. Results: Scientific Publications show that the restricted solubility of this compound can be circumvented by delivery systems for non-conventional, such as vesicular systems, inclusion complexes or solid dispersions. Conclusion: These technologies allow for pharmaceutical forms more stable and soluble bioavailability less variable.

To determine the accuracy of multiplex real-time PCR (Anyplex™ II MTB/MDR kit) in detecting Isoniazid (INH)- and Rifampin (RIF)-resistant Mycobacterium tuberculosis strains from various clinical specimens. The performance of Anyplex™ II MTB/MDR kit in detecting INH- and RIF-resistant M. tuberculosis compared to the conventional drug susceptibility tests by Mycobacterial Growth Indicator Tube (MGIT). A total of 430 clinical samples had positive results for M. tuberculosis from both Anyplex™ II MTB/MDR kit assay and mycobacterial cultures by MGIT method. When compared to MGITs, the sensitivity and specificity of Anyplex™ II MTB/MDR kit in detecting INH-resistant TB were 85.71% and 99.75%, respectively. For the detection of MDR-TB, the sensitivity and specificity of the test were 82.35% and 99.76%, respectively. The positive predictive values and negative predictive values to detect INH-resistant TB were 96.77% and 98.75%, respectively. Anyplex™ II MTB/MDR kit can be used to rapidly de...

Rifampicin (RIF) films were prepared. X-ray diffraction (XRD) patterns showed monoclinic structure of powder Rifampicin. While XRD patterns showed nanocrystalline structure of the thin films. The nanostructure character of Rifampicin films is confirmed by using high resolution transmission electron microscope (HRTEM). Spectrophotometric method was used to measure the intensity of transmitted and reflected light in Rifampicin films to determine optical parameters. The allowed indirect transitions are found in Rifampicin films with energy gap of 1.9 eV. I-V characteristics of Au/Rifampicin/p-Si/Al were measured in different conditions. Under illumination, the device shows photoinduced charge transfer which suggests that, the fabricated device can be used as photodiode. The value of photoresponsivity of the diode is increases with increasing light intensity.

The present study was aimed at developing and exploring the use of mannosylated dendritic architecture for the selective delivery of an anti-tuberculosis drug, rifampicin (RIF) to alveolar macrophages (AM). The mannosylated dendritic architecture was synthesized and characterized by using IR and NMR spectroscopy. RIF was efficiently loaded into mannosylated dendrimer using dissolution method. Various physicochemical and physiological parameters such as UV, SEM, DSC, drug loading, solubilization, pH dependent in-vitro release, hemolytic toxicity, phagocytic AM uptake and cytotoxicity concerning the mannosylated dendrimer were evaluated. RIF loaded mannosylated dendrimer reduced release rate of drug in pH 7.4, hemolytic toxicity and cytotoxicity; whereas enhanced drug release in pH 5.0 and AM uptake was observed. The present novel dendritic system displayed suitability in terms of biocompatibility and site-specific delivery of antitubercular drug RIF.

Tuberculosis therapy remains a challenge even today, mainly due to the problems of bacterial resistance, side effects and low patient compliance, associated with anti-tubercular drugs. A bioenhancer is an agent capable of enhancing bioavailability and bioefficacy of a particular drug with which it is combined, without any typical pharmacological activity of its own at the dose used. Microspheres are one of the multiparticulate drug delivery systems prepared to obtain prolonged drug delivery, to improve its bioavailability or stability and to target drug to specific sites. Rifampicin is an important component of fixed dose combination used in first line therapy of tuberculosis. In the present study, we attempted an innovative approach to overcome the above-mentioned problems of tuberculosis therapy by combining both these approaches of microspheres and bioenhancers. Small amount of herbal extract of Piper nigrum were incorporated as a bioenhancer in variable amount for each dose of r...

RP-HPLC method has been developed and validated for assay to three of four constituents in anti-tuberculosis 4-FDC tablet simultaneously: rifampicin, isoniazid and pyrazinamid. To increase UV absorbance of the three components, phenyl isothiocyanate (PITC) is used in pre-column derivatization. Derivatization parameters were optimized and the results are molar ratio of the analytes to PITC, 1:40 and time for vortex processing is 60 seconds. Derivatization result was separated using stationary phase Phenomenex Luna C 18 , 5 µm (250 x 4.6 mm). Phosphate buffer 8 mM pH 4.8 and acetonitrile were used as mobile phase with gradient system, flow rate 1.0 mL/minute and detector UV 254 nm. This method was validated with some parameters: selectivity, linearity, precision, accuracy, LOD, LOQ and stability. This method cannot be performed on a compound of ethambutol because its reaction produced two derivatives. So this method can only be applied to assay to three constituent in anti-tuberculosis 4-FDC tablet simultaneously.

Nanoparticles (NPs) are increasingly used as biodegradable vehicles to selectively deliver therapeutic agents such as drugs or antigens to cells. The most widely used vehicle for this purpose is based on co-polymers of lactic acid and glycolic acid (PLGA) -that has been extensively used in experiments aimed at delivering antibiotics against Mycobacterium tuberculosis in animal models of tuberculosis.

Multidrug-resistant (MDR) tuberculosis (TB) poses an important challenge in TB management and control. Rifampicin resistance (RR) is a solid surrogate marker of MDR-TB. We investigated the RR-TB clustering rates, bacterial population dynamics to infer transmission dynamics, and the impact of changes to patient management on these dynamics over 27 years in Rwanda. We analysed whole genome sequences of a longitudinal collection of nationwide RR-TB isolates. The collection covered three important periods: before programmatic management of MDR-TB (PMDT; 1991-2005), the early PMDT phase (2006-2013), in which rifampicin drug-susceptibility testing (DST) was offered to retreatment patients only, and the consolidated phase (2014-2018), in which all bacteriologically confirmed TB patients had rifampicin DST done mostly via Xpert MTB/RIF assay. We constructed clusters based on a 5 SNP cut-off and resistance conferring SNPs. We used Bayesian modelling for dating and population size estimations, TransPhylo to estimate the number of secondary cases infected by each patient, and multivariable logistic regression to assess predictors of being infected by the dominant clone. Of 308 baseline RR-TB isolates considered for transmission analysis, the clustering analysis grouped 259 (84.1%) isolates into 13 clusters. Within these clusters, a single dominant clone was discovered containing 213 isolates (82.2% of clustered and 69.1% of all RR-TB), which we named the "Rwanda Rifampicin-Resistant clone" (R3clone). R3clone isolates belonged to Ugandan sub-lineage 4.6.1.2 and its rifampicin and isoniazid resistance were conferred by the Ser450Leu mutation in rpoB and Ser315Thr in katG genes, respectively. All R3clone isolates had Pro481Thr, a putative compensatory mutation in the rpoC gene that likely restored its fitness. The R3clone was estimated to first arise in 1987 and its population size increased exponentially through the 1990s', reaching maximum size (∼84%) in early 2000 s', with a declining trend since 2014. Indeed, the highest proportion of R3clone (129/157; 82·2%, 95%CI: 75·3-87·8%) occurred between 2000 and 13, declining to 64·4% (95%CI: 55·1-73·0%) from 2014 onward. We showed that patients with R3clone detected after an unsuccessful category 2 treatment were more likely to generate secondary cases than patients with R3clone detected after an unsuccessful category 1 treatment regimen. RR-TB in Rwanda is largely transmitted. Xpert MTB/RIF assay as first diagnostic test avoids unnecessary rounds of rifampicin-based TB treatment, thus preventing ongoing transmission of the dominant R3clone. As PMDT was intensified and all TB patients accessed rifampicin-resistance testing, the nationwide R3clone burden declined. To our knowledge, our findings provide the first evidence supporting the impact of universal DST on the transmission of RR-TB.

The cases are reported of two infants with pneumococcal meningitis in whom initial antibiotic treatment was ineffective despite the organisms being sensitive to the drugs used. A clinical and radiological diagnosis of meningoencephalitis was made. A rapid improvement followed the addition of rifampicin treatnent.

Background The Global Laboratory Initiative (GLI) guidelines recommend repeat for GeneXpertMTB/RIF (XpertMTB/RIF) in patients with a low pretest probability of rifampicin resistance (RR). Methods This was a cross-sectional study using results of sputum specimens collected from participants screened for the STREAM 2 trial. We recruited all patients with XpertMTB/RIF RR-TB detected who were referred for RR/multidrug-resistant (MDR) TB treatment initiation at Mulago National Referral Hospital, Kampala, between September 2017 and October 2019. At baseline, smear microscopy, repeat XpertMTB/RIF, Xpert Ultra, and MTBDRplus assays were done on sputum specimens. Culture-based drug susceptibility testing (DST) was performed on discordant specimens. We analyzed the prevalence and factors associated with discordance between initial and repeat XpertMTB/RIF RR and false XpertMTB/RIF RR. False XpertMTB/RIF RR was defined as no RR detected by any of Xpert Ultra, LPA, or culture DST (reference comp...

Background GeneXpert MTB/RIF (Xpert) and Genotype MTBDRplus (DRplus) are two World Health Organization (WHO) endorsed probe based molecular drug susceptibility testing (DST) methods for rapid diagnosis of drug resistant tuberculosis. Both methods target the same 81 bp Rifampicin Resistance Determining Region (RRDR) of bacterial RNA polymerase β subunit (rpoB) for detection of Rifampicin (RIF) resistance associated mutations using DNA probes. So there is a correspondence of the probes of each other and expected similarity of probe binding. Methods We analyzed 92 sputum specimens by Xpert, DRplus and LJ proportion method (LJ-DST). We compared molecular DSTs with gold standard LJ-DST. We wanted to see the agreement level of two molecular methods for detection of RIF resistance associated mutations. The 81bp RRDR region of rpoB gene of discrepant cases between the two molecular methods was sequenced by Sanger sequencing. Results The agreement of Xpert and DRplus with LJ-DST for detection of RIF susceptibility was found to be 93.5% and 92.4%, respectively. We also found 92.4% overall agreement of two molecular methods for the detection of RIF susceptibility. A total of 84 out of 92 samples (91.3%) had agreement on the molecular locus of RRDR mutation by DRplus and Xpert. Sanger sequencing of 81bp RRDR revealed that Xpert probes detected seven of eight discrepant cases correctly and DRplus was erroneous in all the eight cases.

Various drugs have been used for the treatment of antitubercular treatment. Such drugs may often lead to
hepatotoxicity.
Aim: To Access the pharmacokinetic profile of rifampicin and isoniazid and metabolites of isoniazid viz. Mono
Acetyl Hydrazine (MAH) and Diacetyl Hydrazine (DAH) in patients of pulmonary tuberculosis which served as control
group and in patients of Antitubercular Drugs (ATD) induce hepatotoxicity.
Materials and methods: Ten patients of pulmonary tuberculosis already receiving ATD for at least last four
weeks and had no clinical hepatotoxicity and ten patients of pulmonary tuberculosis suffering from ATD induced
hepatotoxicity were included. Liver Function Test Serum bilirubin, SGOT, SGPT, Serum Alkaline phosphatase,
Prothrombin time, HbsAg, IgM anti HBc for hepatitis B, blood urea and serum creatinine were investigated.
Results: Patients suffering from ATD induced hepatotoxicity have shown increased peak serum Conc. t1/2 and
decrease in serum clearance of INH and increase in peak serum concentration, AUC & decrease clearance of RMP
indicating that there was delayed elimination of both the drugs (RMP, INH) which may further cause hepatotoxicity.
Conclusion: It was concluded that in patients of liver derangement low dose of INH and rifampicin should be
given and plasma levels of MAH may act as an indicator to predict hepatotoxicity in patients receiving antitubercular
treatment

Nanoparticles (NPs) are increasingly used as biodegradable vehicles to selectively deliver therapeutic agents such as drugs or antigens to cells. The most widely used vehicle for this purpose is based on copolymers of lactic acid and glycolic acid (PLGA) and has been extensively used in experiments aimed at delivering antibiotics against Mycobacterium tuberculosis in animal models of tuberculosis. Here, we describe fabrication of PLGA NPs containing either a high concentration of rifampicin or detectable levels of the green fluorescent dye, coumarin-6. Our goal here was twofold: first to resolve the controversial issue of whether, after phagocytic uptake, PLGA NPs remain membrane-bound or whether they escape into the cytoplasm, as has been widely claimed. Second, we sought to make NPs that enclosed sufficient rifampicin to efficiently clear macrophages of infection with Mycobacterium bovis BCG. Using fluorescence microscopy and immuno-electron microscopy, in combination with markers for lysosomes, we show that BCG bacteria, as expected, localized to early phagosomes, but that at least 90% of PLGA particles were targeted to, and remained in, low pH, hydrolaserich phago-lysosomes. Our data collectively argue that PLGA NPs remain membrane-enclosed in macrophages for at least 13 days and degrade slowly. Importantly, provided that the NPs are fabricated with sufficient antibiotic, one dose given after infection is sufficient to efficiently clear the BCG infection after 9-12 days of treatment, as shown by estimates of the number of bacterial colonies in vitro.

SETTING: To assess the revised World Health Organization-recommended dose of 10–20 mg/kg rifampicin (RMP), we studied the steady state pharmacokinetics of RMP in South African children who received standard treatment for drug-susceptible tuberculosis (TB). OBJECTIVE: To determine the formulation effect on the pharmacokinetics of RMP. DESIGN: RMP plasma concentrations were characterised in 146 children (median age 1.4 years, range 0.2–10.2). The morning dose on the day of the pharmacokinetic evaluation was administered as one of two RMP single-drug oral suspensions. RESULTS: While one formulation achieved 2 h concentrations in the range of those observed in adults (median 6.54 mg/l, interquartile range [IQR] 4.47–8.84), the other attained a median bioavailability of only 25% of this, with a median 2 h concentration of 1.59 mg/l (IQR 0.89–2.38). CONCLUSION: RMP is a key drug for the treatment of TB. It is critical that the quality of RMP suspensions used to treat childhood TB is ensured.

Nanoparticles (NPs) are increasingly used as biodegradable vehicles to selectively deliver therapeutic agents such as drugs or antigens to cells. The most widely used vehicle for this purpose is based on copolymers of lactic acid and glycolic acid (PLGA) and has been extensively used in experiments aimed at delivering antibiotics against Mycobacterium tuberculosis in animal models of tuberculosis. Here, we describe fabrication of PLGA NPs containing either a high concentration of rifampicin or detectable levels of the green fluorescent dye, coumarin-6. Our goal here was twofold: first to resolve the controversial issue of whether, after phagocytic uptake, PLGA NPs remain membrane-bound or whether they escape into the cytoplasm, as has been widely claimed. Second, we sought to make NPs that enclosed sufficient rifampicin to efficiently clear macrophages of infection with Mycobacterium bovis BCG. Using fluorescence microscopy and immuno-electron microscopy, in combination with markers for lysosomes, we show that BCG bacteria, as expected, localized to early phagosomes, but that at least 90% of PLGA particles were targeted to, and remained in, low pH, hydrolaserich phago-lysosomes. Our data collectively argue that PLGA NPs remain membrane-enclosed in macrophages for at least 13 days and degrade slowly. Importantly, provided that the NPs are fabricated with sufficient antibiotic, one dose given after infection is sufficient to efficiently clear the BCG infection after 9-12 days of treatment, as shown by estimates of the number of bacterial colonies in vitro.