Time-dependent pharmacokinetic interaction between zidovudine and rifampicin following oral administration at 10.00 and 22.00 hours.
Rifampicin, an antitubercular agent, is a known metabolic inducer. Previous studies have suggested that rifampicin may interfere with the pharmacokinetics of oral zidovudine when the two drugs are co-administered. Circadian variations in the pharmacokinetics of rifampicin have been reported. We report here a circadian influence on the pharmacokinetics of zidovudine in the presence of rifampicin when administered orally in rabbits. Either zidovudine or zidovudine with rifampicin was administered orally at 10.00 or 22.00 h to 12 healthy rabbits in a randomized cross-over study. Serum zidovudine was estimated by HPLC. A significant (p <0.05) lowering of Cmax, (1/2), AUC(0-6h) and MRT was observed following zidovudine and rifampicin co-administration compared to zidovudine alone at 10.00 h. Accordingly clearance increased to a significant extent. However, such an interaction effect was masked following administration at 22.00 h. The time-dependent influence of rifampicin on the pharmacokinetics of zidovudine may be due to time-dependent changes in absorption and elimination of rifampicin, thus modifying its induction effect on the levels of UDP glucuronyl transferase and cytochrome P-450 content in liver which are responsible for metabolism of zidovudine.
Karwa
R
R
University College of Pharmaceutical Sciences, Kakatiya University, Warangal, India.
Shashank
A
A
Rambhau
D
D
Gopinath
D
D
Ravi
D
D
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D019454:Chronotherapy; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D015215:Zidovudine; D012293:Rifampin