Impaired absorption of zidovudine in patients with AIDS-related small intestinal disease

Objectives: To investigate the effect of small intestinal disease (SID) on the absorption of zidovudine (ZDV) in patients with AIDS. Methods: Fourteen fasted homosexual men with AIDS received a single oral dose of ZDV (5 mg/kg). Nine subjects had clinical evidence of intestinal disease (chronic diarrhoea with wasting) confirmed by reduced fat absorption measured indirectly using the C-14-triolein test. Five subjects had AIDS-related symptoms other than those affecting the gastrointestinal tract with normal fat absorption. Sequential measurements of plasma ZDV including its glucuronide metabolite (GZDV) were obtained using radioimmunoassay and ZDV/GZDV concentrations-time profiles of both groups of subjects were compared. Comparisons were also made for each of the following computed variables: the maximum plasma concentration (C-max), time to reach C-max (T-max), area under the plasma concentration-time curve (AUG(0-6 h)), the elimination half-life (t(1/2)), and apparent oral clearance (CL(0)). Results: in patients with SID, C-max ZDV was reduced (6.39 +/- 3.39 versus 11.51 +/- 5.01 mu mol/l; P < 0.05) and T-max ZDV prolonged (0.81 +/- 0.51 versus 0.40 +/- 0.14 h; P < 0.05) but AUC(0-6 h) ZDV was no different from the non-SID group (8.03 +/- 2.73 versus 14.56 +/- 9.0 mu mol/l(-1) xh; P = 0.06). There were no differences in t(1/2) ZDV (1.22 +/- 0.20 Versus 1.13 +/- 0.30 h) or CL(0) ZDV (3017 +/- 1158 versus 1700 +/- 889 ml/min; P> 0.05) between SID and non-SID groups, respectively, and GZDV values were comparable between the two groups. Conclusion: These data suggest delayed absorption rather than altered metabolism of ZDV in AIDS-related SID and raise the possibility of drug malabsorption. The clinical efficacy of orally administered low-dose ZDV regimens may require further evaluation in patients with chronic diarrhoea and AIDS.