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  • Title: Impaired absorption of zidovudine in patients with AIDS-related small intestinal disease.
    Author: Kapembwa MS, Fleming SC, Orr M, Wells C, Bland M, Back D, Griffin GE.
    Journal: AIDS; 1996 Nov; 10(13):1509-14. PubMed ID: 8931785.
    Abstract:
    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 14C-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 radio-immunoassay 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 (Cmax), time to reach Cmax (Tmax), area under the plasma concentration-time curve (AUC0-6 h), the elimination half-life (t 1/2), and apparent oral clearance (CL0). RESULTS: In patients with SID, Cmax ZDV was reduced (6.39 +/- 3.39 versus 11.51 +/- 5.01 mumol/l; P < 0.05) and Tmax ZDV prolonged (0.81 +/- 0.51 versus 0.40 +/- 0.14 h; P < 0.05) but AUC0-6 h ZDV was no different from the non-SID group (8.03 +/- 2.73 versus 14.56 +/- 9.0 mumol/l-1xh; P = 0.06). There were no differences in t 1/2 ZDV (1.22 +/- 0.20 versus 1.13 +/- 0.30 h) or CL0 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. CONCLUSIONS: 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.
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