Canadian multicenter azidothymidine trial: Azt pharmacokinetics

The study objective was to describe the pharmacokinetics of azidothymidine (AZT) in a large population of early, asymptomatic human immunodeficiency virus (HlV)-infected individuals. The study design was a multicenter, prospective, descriptive single-dose pharmacokinetic study. Each of 66 fasting, male, HIV-infected homosexuals older than 18 years of age and in CDC classifications II, III, and IVC2 received a single 400-mg oral dose of AZT with subsequent pharmacokinetic measurements performed during an 8-h period for AZT and its major metabolite, glucuronylazidothymidine (GAZT). Results were obtained in 65 patients (36 smokers, 29 nonsmokers), of whom 3 were noted to have hepatic dysfunction. In those with normal hepatic function, the following parameters were described: AZT, area under the curve (AUC) ± SD, 9.9 ± 5.7 p.M • h, maximum concentration (C_max) ± SD, 7.3 ± 4.7 \lM; time to maximum concentration (T_max) ± SD, 0.93 ± 0.42 h, and half-life (t_l/2) ± SD, 1.0 ± 0.8 h. Corresponding values for GAZT were: AUC ± SD 35.7 ± 10.3 pM ■ h, C_max ± SD 21.3 ±7.3 pM, T_max ± SD 1.2 ± 0.50 h, t_1/2 ± SD 0.98 ± 0.62 h, No significant differences were found in comparisons of study site, CDC classification of disease, smokers versus nonsmokers, and in patients with hepatic dysfunction, although a higher AUC and earlier C_max for AZT was noted in the latter group. It is concluded that AZT pharmacokinetics are similar in patients with early asymptomtic HIV disease when compared with previous reports in patients with later disease. This study finds no difference in pharmacokinetics of AZT in smokers versus nonsmokers and suggests a trend to a decreased presystemic elimination in patients with hepatic dysfunction.