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±2l·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. © 1993 The British Society for Antimicrobial Chemotherapy.