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- W2034227821 abstract "To study the effect of rifampin (INN, rifampicin), a potent inducer of cytochrome P450, on the steady-state pharmacokinetics of delavirdine.Twelve patients who were positive for human immunodeficiency virus, with CD4 counts ranging from 110 to 483/mm3, were randomized to two groups and studied in parallel. Both the control group (n = 5) and the rifampin group (n = 7) received 400 mg delavirdine mesylate every 8 hours for 30 days; subjects in the rifampin group took a 600 mg once-daily dose of rifampin on days 16 through 30. Harvested plasma from serial blood samples collected after dosing on days 15, 16, and 30 was assayed for delavirdine and its N-desalkyl metabolite concentrations with a reversed-phase HPLC method. Blood samples obtained on days 16 and 30 were also assayed for rifampin by HPLC.Delavirdine mesylate alone and in combination with rifampin was well tolerated. On day 30, statistically significant differences between groups were observed for all delavirdine pharmacokinetic parameters (p < 0.049). In the rifampin group, delavirdine oral clearance increased by about 27-fold (p = 0.022), resulting in virtually negligible (< 0.09 mumol/L) steady-state through drug concentrations in all patients after 2 weeks of concurrent dosing of delavirdine mesylate and rifampin. The ratio of metabolite formation to elimination clearance for desalkyldelavirdine was significantly higher (3.9 +/- 1.2 versus 0.23 +/- 0.10) and delavirdine elimination half-life was significantly shorter (1.7 +/- 1.4 versus 4.3 +/- 1.3 hours) when delavirdine mesylate was taken with rifampin. Rifampin pharmacokinetic parameters on days 16 and 30 were similar to those previously reported for normal volunteers.The findings of this study indicate that rifampin induces the metabolism of delavirdine. Therefore therapy with rifampin is contraindicated in patients receiving delavirdine mesylate." @default.
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- W2034227821 date "1997-05-01" @default.
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- W2034227821 title "Pharmacokinetic study of the interaction between rifampin and delavirdine mesylate*" @default.
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- W2034227821 doi "https://doi.org/10.1016/s0009-9236(97)90134-x" @default.
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