A study of the pharmacokinetics of azithromycin and nelfinavir when coadministered in healthy volunteers

A two-way, open-label, crossover study in 12 subjects was undertaken to stu dy the potential for azithromycin to alter the pharmacokinetics of nelfinav ir and/or its active metabolite, MB. A secondary objective was to character ize any potential interaction that nelfinavir may have with azithromycin. D uring one dosing arm, subjects received a single 1200 mg oral dose of azith romycin. During the other, subjects received 11 days of nelfinavir 750 mg q 8h with a single 1200 mg oral dose of azithromycin given concurrently with the Day 9 morning nelfinavir dose. Serum samples were collected after each azithromycin dose for 168 hours and after the Day 8 and 9 morning nelfinavi r doses for 8 hours to characterize azithromycin, nelfinavir, and M8 pharma cokinetic parameters during both control and test periods. Both dosing regi mens were well tolerated, rr ith only mild to moderate GI side effects bein g the most frequently reported. Azithromycin n as found to cause a statisti cally, though nor clinically, significant decrease in nelfinavir and M8 exp osures. In contrast, nelfinavir caused azithromycin C-max and exposure (AUC ) values to increase by > 100%. Inhibition of p-glycoprotein by nelfinavir may be responsible for this significant interaction. This increase in azith romycin exposure has the potential to increase clinical antibacterial effic acy without significantly increasing gastrointestinal side effects, though the impact on other systemic sites needs to be studied. (C) 2000 the Americ an College of Clinical Pharmacology.