TY - JOUR
T1 - The Effect of Cimetidine and Ranitidine Administration With Zidovudine
AU - Fletcher, Courtney V.
AU - Henry, W. Keith
AU - Noormohamed, Saleem E.
AU - Rhame, Frank S.
AU - Balfour, Henry H
PY - 1995
Y1 - 1995
N2 - Study Objective. To evaluate the possibility of a drug interaction with zidovudine and histamine2‐receptor antagonists in individuals infected with the human immunodeficiency virus. Design. Randomized crossover study. Setting. University‐affiliated research center. Patients. Six HIV‐infected individuals. Interventions. 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. Measurements and 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 given with cimetidine. In the presence of cimetidine the urinary excretion of zidovudine decreased from 89.5 to 53.7 μM (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 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. 1995 Pharmacotherapy Publications Inc.
AB - Study Objective. To evaluate the possibility of a drug interaction with zidovudine and histamine2‐receptor antagonists in individuals infected with the human immunodeficiency virus. Design. Randomized crossover study. Setting. University‐affiliated research center. Patients. Six HIV‐infected individuals. Interventions. 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. Measurements and 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 given with cimetidine. In the presence of cimetidine the urinary excretion of zidovudine decreased from 89.5 to 53.7 μM (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 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. 1995 Pharmacotherapy Publications Inc.
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U2 - 10.1002/j.1875-9114.1995.tb02885.x
DO - 10.1002/j.1875-9114.1995.tb02885.x
M3 - Article
C2 - 8602376
AN - SCOPUS:0028869116
SN - 0277-0008
VL - 15
SP - 701
EP - 708
JO - Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
JF - Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
IS - 6
ER -