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-state 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.) pharmacokinetic parameters were determined on day 1 and during chronic therapy, respectively: Cmax (4.09 +/- 2.54 vs 3.82 +/- 1.03 mumol l-1), oral clearance (40.7 +/- 12.9 vs 41.1 +/- 8.4 ml min-1 kg-1) and terminal half-life (68.4 +/- 29.4 vs 65.1 +/- 13.1 min). Mean pharmacokinetic parameters 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 Cmax could be detected with a power of 80% at the 5% significance level. Intra-subject coefficients of variation were 17% for clearance and 32% for Cmax, respectively. This study suggests that within a group of patients whose stage of HIV infection and general health are relatively stable, first-dose pharmacokinetic parameters provide a good estimate of multiple-dose pharmacokinetic parameters.
Bureau of Drug Research, Health & Welfare Canada, Ottawa.
K
K
Gallicano
J
J
Sahai
E
E
Ormsby
D W
DW
Cameron
A
A
Pakuts
I
I
McGilveray
D000284:Administration, Oral; D000328:Adult; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006207:Half-Life; D006716:Homosexuality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D015215:Zidovudine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D015215:Zidovudine