Pharmacokinetic study of the interaction between rifampin and delavirdine mesylate

摘要: Objective To study the effect of rifampin (INN, rifampicin), a potent inducer cytochrome P450, on steady-state pharmacokinetics delavirdine. Methods Twelve patients who were positive for human immunodeficiency virus, with CD4 counts ranging from 110 to 483/mm3, randomized two groups and studied in parallel. Both control group (n = 5) 7) received 400 mg delavirdine mesylate every 8 hours 30 days; subjects took 600 once-daily dose days 16 through 30. Harvested plasma serial blood samples collected after dosing 15, 16, was assayed its N-desalkyl metabolite concentrations reversed-phase HPLC method. Blood obtained also by HPLC. Results Delavirdine alone combination well tolerated. On day 30, statistically significant differences between observed all pharmacokinetic parameters (p < 0.049). In group, oral clearance increased about 27-fold 0.022), resulting virtually negligible (<0.09 μmol/L) trough drug 2 weeks concurrent rifampin. The ratio formation elimination desalkyldelavirdine significantly higher (3.9 ± 1.2 versus 0.23 0.10) half-life shorter (1.7 1.4 4.3 1.3 hours) when taken Rifampin similar those previously reported normal volunteers. Conclusions The findings this indicate that induces metabolism delavirdine. Therefore therapy is contraindicated receiving mesylate. Clinical Pharmacology & Therapeutics (1997) 61, 544–553; doi: