Erratic zidovudine bioavailability in HIV seropositive patients.
The bioavailability of zidovudine was evaluated in 16 HIV seropositive patients using a prospective standardized study. Symptomatology, D-xylose absorption and immune status were also measured to determine indicators of poor bioavailability. Zidovudine was rapidly absorbed (Tmax: 0.82 +/- 0.39 h) with a large variation in peak serum concentrations (Cmax: 1.21 +/- 0.64 mg/L). The mean elimination half-lives after intravenous and oral administration were 1.5 +/- 0.4 h and 1.3 +/- 0.2 h, respectively. Mean zidovudine bioavailability was 64.0 +/- 21.3% and was not associated with D-xylose absorption values. Five h urine D-xylose excretion was abnormal in seven patients but only three (43%) had zidovudine bioavailabilities below the mean for the group. Conversely, only five of nine patients (56%) with normal D-xylose absorption tests had zidovudine absorption values below the mean. The presence of a mild alteration in bowel habits, defined as up to four unformed or semi-solid stools per day, showed a highly significant relationship to low bioavailability (P < 0.0001, Student's t-test). Lower CD4 lymphocyte counts were also associated with a low bioavailability (R-squared, 0.36, P = 0.0143). Patients with lower CD4 lymphocyte counts or with mild diarrhoea may be at risk for erratic zidovudine absorption.
Macnab
K A
KA
Department of Medicine, University of Calgary, Alberta, Canada.
Gill
M J
MJ
Sutherland
L R
LR
De Boer Visser
N
N
Church
D
D
D000328:Adult; D001682:Biological Availability; D015496:CD4-Positive T-Lymphocytes; D015658:HIV Infections / Q000378:metabolism*; D006679:HIV Seropositivity / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011897:Random Allocation; D015215:Zidovudine / Q000493:pharmacokinetics*
D015215:Zidovudine