Pharmacokinetic study of the interaction between rifampin and delavirdine mesylate

• Published in: Clinical pharmacology and therapeutics 1997-05, Vol.61 (5), p.544-553
• Main Authors: Borin, Marie T., Chambers, James H., Carel, Barbara J., Gagnon, Suzanne, Freimuth, William W.
• Format: Article
• Language: English
• Subjects: Adult; Alkylation; Anti-HIV Agents - blood; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - therapeutic use; Antibiotics, Antitubercular - administration & dosage; Antibiotics, Antitubercular - blood; Antibiotics, Antitubercular - pharmacokinetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Aryl Hydrocarbon Hydroxylases; Biological and medical sciences; Blotting, Western; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System - drug effects; Cytochrome P-450 Enzyme System - metabolism; Delavirdine; Dose-Response Relationship, Drug; Drug Interactions; Female; HIV Seropositivity - blood; HIV Seropositivity - drug therapy; HIV Seropositivity - metabolism; Humans; Hydrocortisone - analogs & derivatives; Hydrocortisone - blood; Indoles - blood; Indoles - pharmacokinetics; Indoles - therapeutic use; Liver - drug effects; Liver - metabolism; Male; Medical sciences; Middle Aged; Oxidoreductases, N-Demethylating - drug effects; Oxidoreductases, N-Demethylating - metabolism; Pharmacology. Drug treatments; Piperazines - blood; Piperazines - pharmacokinetics; Piperazines - therapeutic use; Reverse Transcriptase Inhibitors - pharmacokinetics; Reverse Transcriptase Inhibitors - therapeutic use; Rifampin - administration & dosage; Rifampin - blood; Rifampin - pharmacokinetics
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1016/S0009-9236(97)90134-X

Objective To study the effect of rifampin (INN, rifampicin), a potent inducer of cytochrome P450, on the steady‐state pharmacokinetics of delavirdine. Methods 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. Results 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 (