Determination of Absolute Bioavailability of Rifampicin by Varying the Mode of Intravenous Administration and the Time of Sampling

Abstract

This study was carried out to determine the true absolute bioavailability value of rifampicin by varying the mode of intravenous administration and the time of sampling. The drug was administered to Laca mice at a dose of 12 mg/kg body weight through oral, intravenous bolus, 30 min infusion and 3 h infusion modes. Sampling was done at rapid initial points of 1 min and 5 min, followed by 15 min, 30 min, 1 h, 2 h, 4 h, 6 h and 8 h. Plasma samples were analyzed by microbiological method, which was validated by comparison with HPLC and LC/MS/MS techniques of analyses. Rifampicin showed >86% absolute bioavailability when oral administration was compared with 30 min or 3 h infusion. However, the values dropped between 44.5 and 57.6% when drug was administered intravenously as a bolus and the samples were taken at rapid initial intervals, i.e., 1 min and 5 min. The absolute bioavailability values increased to >94% when these initial samples were skipped. The study reveals that rifampicin has only ∼50% absolute bioavailability, if the basic principles of pharmacokinetics of bolus intravenous administration and rapid sampling points are employed. The relevance of the study is discussed with respect to the determination of the permeability class of the drugs and their categorization into the Biopharmaceutics Classification System (BCS), currently under focus for the grant of biowaivers by the USFDA.

Key words: :

• Rifampicin
• Absolute oral bioavailability
• Bolus
• Infusion
• Sampling schedule
• BCS

Notes

[29] FDA, Guidance for Industry: Waiver of in-vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system. US Department of Health and Human Services, Food and Drug Administration, Centre of Drug Evaluation and Research, 2000.