THE EFFECT OF CIMETIDINE AND RANITIDINE ADMINISTRATION WITH ZIDOVUDINE

Study Objective. To evaluate the possibility of a drug interaction wit h zidovudine and histamine(2)-receptor antagonists in individuals infe cted with the human immunodeficiency virus. Design. Randomized crossov er study. Setting. University-affiliated research center. Patients. Si x HIV-infected individuals. Interventions. The subjects received 7-day regimens of zidovudine 600 mg/day alone, zidovudine with cimetidine 1 200 mg/day, and zidovudine with ranitidine 300 mg/day. Measurements an d Main 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 give n with cimetidine. In the presence of cimetidine the urinary excretion of zidovudine decreased from 89.5 to 53.7 mu M (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). Conclusion. Cimetidine presumably inhibits th e renal clearance of zidovudine by competing for tubular secretion. Ba sed on the observation that neither cimetidine nor ranitidine had a si gnificant effect on serum concentrations of zidovudine or zidovudine g lucuronide, a change in the dosage of zidovudine is not warranted.