The effect of cimetidine and ranitidine administration with zidovudine.
OBJECTIVE
To evaluate the possibility of a drug interaction with zidovudine and histamine2-receptor antagonists in individuals infected with the human immunodeficiency virus.


METHODS
Randomized crossover study.


METHODS
University-affiliated research center.


METHODS
Six HIV-infected individuals.


METHODS
The subjects received 7-day regimens of zidovudine 600 mg/day alone, zidovudine with cimetidine 1200 mg/day, and zidovudine with ranitidine 300 mg/day.


RESULTS
The renal clearance of zidovudine when given alone was 0.41 L/kg/hour, and was reduced to 0.18 L/kg/hour (p = 0.002) when given with cimetidine. In the presence of cimetidine the urinary excretion of zidovudine decreased from 89.5 to 53.7 microM (p = 0.01), the urinary ratio of metabolite to parent increased from 5.16 to 9.96 (p = 0.0001), and the fraction of zidovudine converted to metabolite increased from 0.86 to 0.92 (p = 0.0025).


CONCLUSIONS
Cimetidine presumably inhibits the renal clearance of zidovudine by competing for tubular secretion. Based on the observation that neither cimetidine nor ranitidine had a significant effect on serum concentrations of zidovudine or zidovudine glucuronide, a change in the dosage of zidovudine is not warranted.
Fletcher
C V
CV
Department of Pharmacy Practice, University of Minnesota Health Sciences Center, Minneapolis 55455, USA.
Henry
W K
WK
Noormohamed
S E
SE
Rhame
F S
FS
Balfour
H H
HH
D000293:Adolescent; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count / Q000187:drug effects*; D016516:CD4-CD8 Ratio / Q000187:drug effects; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D011899:Ranitidine / Q000008:administration & dosage / Q000494:pharmacology*; D015215:Zidovudine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000897:Anti-Ulcer Agents; D000998:Antiviral Agents; D006635:Histamine H2 Antagonists; D015215:Zidovudine; D002927:Cimetidine; D011899:Ranitidine; C055886:3'-azido-3'-deoxy-5'-O-beta-glucopyranuronosylthymidine