Pharmacokinetics of zidovudine alone and in combination with oxazepam in the HIV infected patient

Abstract

This three-phase study was designed to determine if a pharmacokinetic drug-drug interaction exists between zidovudine and oxazepam. Six individuals infected with human immunodeficiency virus (HIV) and receiving zidovudine at 500 mg daily, with normal renal and hepatic function, were enrolled. During phase I, zidovudine pharmacokinetics were studied after steady-state oral administration (100 mg every 4 h) and after a single dose (70 mg) of intravenous zidovudine. Phase II consisted of a single oral dose (30 mg) of oxazepam followed by a 48-h blood sampling period. Phase III began with 48 h of concomitant zidovudine, 100 mg orally every 4 h, and oxazepam, 15 mg orally every 8 h, followed by concomitant dosing of intravenous zidovudine and oral oxazepam. Zidovudine concentrations were determined by radioimmunoassay. Oxazepam concentrations were determined with use of a fluorescence polarization immunoassay. The calculated bioavailability was 0.61 for zidovudine alone and 0.75 when administered in combination with oxazepam (p = 0.16). Plasma half-life for oral zidovudine alone and in combination with oxazepam was 1.17 h versus 0.99 h, respectively (p = 0.25), and 1.38 h versus 1.15 h (p = 0.38) for intravenous zidovudine during single and combination therapy, respectively. Total body clearance of zidovudine was not significantly altered by oxazepam (93 L/h vs. 109 L/h, p = 0.16). The mean pharmacokinetic parameters determined for a single 30-mg dose of oxazepam for oral clearance, apparent volume of distribution, and plasma half-life were 9.8 L/h, 65.7 L, and 5.1 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)