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Pharmacokinetic interaction between amprenavir and delavirdine after multiple‐dose administration in healthy volunteers
Author(s) -
Justesen Ulrik S.,
Klitgaard Niels A.,
Brosen Kim,
Pedersen Court
Publication year - 2003
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2003.01734.x
Subject(s) - amprenavir , pharmacokinetics , medicine , pharmacology , adverse effect , drug interaction , chemistry , biochemistry , hiv 1 protease , protease , enzyme
Aims To evaluate the safety and the pharmacokinetic interaction between amprenavir and delavirdine after multiple dose administration in healthy volunteers. Methods This was a prospective, open‐label, randomized, controlled, two‐sequence, two‐period multiple dose study with 18 healthy subjects. Volunteers were randomly assigned to amprenavir, 600 mg twice a day, or delavirdine, 600 mg twice a day, for 10 days, followed by both drugs for another 10 days with pharmacokinetic evaluation on day 10 and day 20. Adverse events were recorded throughout the study. Results Amprenavir decreased all the delavirdine pharmacokinetic parameters apart from t max . Delavirdine C 12h dropped from 7916 to 933 ng ml −1 (median decrease 5930 ng ml −1 , 95% CI 3013, 8955 ng ml −1 ). A decrease in amprenavir t ½ was also seen leading to almost identical median amprenavir C 24h values. No serious clinical adverse events were observed during the study. The most frequently reported effects were gastrointestinal symptoms, headache, fatigue and rash. Conclusions Amprenavir is an effective inducer of delavirdine metabolism, probably through its effect on hepatic CYP3A4. This could have consequences in other drug‐drug interaction situations. Delavirdine is an inhibitor of amprenavir metabolism. The regimen of amprenavir 600 mg and delavirdine 600 mg twice a day is not recommended when an antiretroviral effect from delavirdine is required.