title: Impaired absorption of zidovudine in patients with AIDS-related small intestinal disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Genitourinary Medicine, Imperial College of Science, St Mary's Hospital Medical School, London, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Kapembwa
authors.forename: S C
authors.initials: SC
authors.lastname: Fleming
authors.forename: M
authors.initials: M
authors.lastname: Orr
authors.forename: C
authors.initials: C
authors.lastname: Wells
authors.forename: M
authors.initials: M
authors.lastname: Bland
authors.forename: D
authors.initials: D
authors.lastname: Back
authors.forename: G E
authors.initials: GE
authors.lastname: Griffin
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D000328:Adult; D002908:Chronic Disease; D003967:Diarrhea / Q000097:blood / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000002:abnormalities*; D008297:Male; D008875:Middle Aged; D014304:Triolein / Q000378:metabolism; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D014304:Triolein; D015215:Zidovudine; C055886:3'-azido-3'-deoxy-5'-O-beta-glucopyranuronosylthymidine