Bioavailability of rifampicin following concomitant administration of ethambutol or isoniazid or pyrazinamide or a combination of the three drugs.

BACKGROUND & OBJECTIVES: Poor bioavailability of rifampicin (R) in combination with other anti-tuberculosis drugs such as isoniazid (H), pyrazinamide (Z), and ethambutol (E) is a subject of much concern for the last few decades. This could be due to an interaction between R and other drugs. An investigation was therefore undertaken to examine the bioavailability of R in the presence of H, Z and E or a combination of the three drugs. METHODS: The study included eight healthy volunteers, each being investigated on four occasions at weekly intervals once with R alone and with three of the four combinations on the three remaining occasions. A partially balanced incomplete block design was employed and the allocation of R or the drug combinations was random. Plasma concentrations of R at intervals up to 12 h were determined by microbiological assay using Staphylococcus aureus as the test organism. The proportion (%) dose of R as R plus desacetyl R (DR) in urine excreted over the periods 0-8 and 8-12 h was also determined. Bioavailability was expressed as an index (BI) of area under time concentration curve (AUC) calculated from the plasma concentrations or proportion of dose of R excreted as R plus DR in urine with the combinations to that with R alone. RESULTS: The bioavailability indices based on AUC were 0.96 with RE, 0.76 with RH, 1.08 with RZ and 0.65 with REHZ. The indices based on urine estimations (0-8 h) were similar, the values being 0.94, 0.84, 0.94 and 0.75, respectively. A second investigation revealed that the decrease of bioavailability of R with H was not due to the excipients present in H tablets. INTERPRETATION & CONCLUSION: Isoniazid alone or in combination with E and Z reduces the bioavailability of R. Urinary excretion data offer a simple and non invasive method for the assessment of bioavailability of R.

Poly (DL-lactide-co-glycolide) microparticles as carriers for antimycobacterial drug rifampicin.

Poly (DL-lactide-co-glycolide) polymers were investigated as carriers for the first line antitubercular drug rifampicin. Different formulations of PLG microparticles viz. porous, non porous and hardened exhibited sustained release of rifampicin up to 7 weeks in vitro. However, hardened PLG microparticles exhibited the most sustained release in vivo in different organs up to 6 weeks. In case of free rifampicin, release was detected in vivo only up to 48 hr. In addition, no hepatotoxicity was observed on a biochemical basis (levels of SGPT, ALP and total bilirubin) in comparison to control animals. Taken together, these results suggest that polymer encapsulated antitubercular drug rifampicin may serve as an ideal therapeutic approach for treatment of tuberculous infections.

The pharmacokinetics of oral rifampicin in AIDS patients.

Previous studies in AIDS patients have shown that the peak serum concentration of rifampicin at 2 hours after administration are below normal ranges. These may be due to malabsorption of the drug resulting in therapeutic failure. However, there is no published data to demonstrate the pharmacokinetics of rifampicin in these AIDS patients. Therefore, the aim of this study was to provide such data. Eight AIDS patients with tuberculosis participated in this study. All patients were scheduled to receive oral rifampicin 600 mg once daily in the morning on an empty stomach. Rifampicin pharmacokinetics were studied on day 14. The mean Cmax was 9.81 +/- 4.41 ug/ml. The mean Tmax was 2.25 +/- 0.71 h. The mean AUC0-24 was 60.25 +/- 36.88 ug.h/ml. The results of our study did not confirm the previous studies. The absorption of rifampicin in most of our AIDS patients were not reduced and delayed. Therefore, rifampicin dosage adjustment for Thai patients may not be necessary.

Serum and cerebrospinal fluid concentrations of rifampicin at two dose levels in children with tuberculous meningitis.

Twenty patients of tuberculous meningitis (TBM) in age group of 6 months to 10 years included in the study were divided into two groups of 10 patients each. Rifampicin was administered in dosage of 10 mg and 7.5 mg/kg bw to each patient of groups I and II respectively. Drug concentrations in serum and CSF of these patients were measured by a microbiological tube dilution method using a strain of Sarcina lutea. In group I mean serum and CSF concentration was 3.84 micrograms/ml and 0.178 microgram/ml respectively, while in group II it was 2.16 micrograms/ml and 0.206 microgram/ml respectively. These concentrations were many times higher than the MIC against Mycobacterium tuberculosis. Mean percentage penetration of rifampicin in CSF was 5 and 10% in group I and II respectively. We recommend similar studies in large number of children before advocating the therapy with low dose of rifampicin in TBM.

El uso de antibióticos en el embarazo: parte I / The use of antibiotics during pregnancy: part I

El empleo de antibióticos durante el embarazo guarda riesgos particulares, siendo los efectos nocivos que pueden resultar del uso de éstos fármacos en la gestación: teratogenicidad, efectos sobre la madre, efectos sobre el curso del embarazo y efectos sobre el feto o el recién nacido. Se ha estimado que la gran mayoría de los antibióticos atraviesan la placenta en grado variable, algunos de ellos son seguros para utilizarse durante el embarazo mientras que algunos otros están completamente contraindicados. Las infecciones severas en la embarazada conllevan un riesgo alto de morbi-mortalidad tanto materna como fetal, sobrepasando en muchos casos el riesgo de los efectos nocivos de los antibióticos, es por ello que en ésta situación las pacientes deben recibir tratamiento antimicrobiano independientemente de los efectos adversos descritos o teóricos, debiendose seleccionar el antibiótico con mayor actividad antimicrobiana y menor riesgo tanto para la madre como para el feto.