PHARMACOKINETICS OF ZIDOVUDINE AFTER THE INITIAL SINGLE-DOSE AND DURING CHRONIC-DOSE THERAPY IN HIV-INFECTED PATIENTS

The pharmacokinetics of zidovudine in 10 symptomatic HIV-infected men were assessed after administration of the initial 200 mg oral dose at the start of therapy (day 1) and on one occasion during non steady-sta te conditions of chronic-dose therapy (200 mg every 4 h while awake on day 21-66; 5 doses per day). The following mean (+/- s.d.) pharmacoki netic parameters were determined on day 1 and during chronic therapy, respectively: C(max) (4.09 +/- 2.54 vs 3.82 +/- 1.03 mumol l-1) oral c learance (40.7 +/- 12.9 vs 41.1 +/- 8.4 ml min-1 kg-1) and terminal ha lf-life (68.4 +/- 29.4 vs 65.1 +/- 13.1 min). Mean pharmacokinetic par ameters on day 1 were < 10% different (P > 0.34) from those determined during chronic therapy. Differences in means of 21% for clearance and 36% for C(max) could be detected with a power of 80% at the 5% signif icance level. Intra-subject coefficients of variation were 17% for cle arance and 32% for Cm., respectively. This study suggests that within a group of patients whose stage of HIV infection and general health ar e relatively stable, first-dose pharmacokinetic parameters provide a g ood estimate of multiple-dose pharmacokinetic parameters.