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Effect of cimetidine on verapamil disposition
Author(s) -
Loi ChoMing,
Rollins Douglas E,
Dukes George E,
Peat Michael A
Publication year - 1985
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1985.106
Subject(s) - cimetidine , verapamil , indocyanine green , volume of distribution , pharmacokinetics , blood flow , distribution (mathematics) , medicine , washout , drug interaction , pharmacology , chemistry , endocrinology , surgery , calcium , mathematical analysis , mathematics
The effects of multiple doses of cimetidine on single‐dose verapamil kinetics were studied in nine healthy men. Baseline hepatic blood flow was estimated by indocyanine green elimination on day 1. On day 2, the subjects received verapamil, 10 mg iv, after which the plasma concentration—time profile was determined. After a 2‐day washout, cimetidine, 300 mg, was taken by mouth four times a day for 5 days. The indocyanine green study was repeated on day 9 and verapamil was taken on day 10. Cimetidine reduced verapamil clearance by 21% and increased the elimination t½ by 50%. The volume of distribution at steady state did not change. Cimetidine increased hepatic blood flow in some subjects, while decreasing it in others. There was no correlation between individual changes in verapamil clearance and hepatic blood flow. These data indicate that cimetidine reduces verapamil clearance by mechanism(s) other than a change in hepatic blood flow or volume of distribution. Clinical Pharmacology and Therapeutics (1985) 37 , 654–657; doi: 10.1038/clpt.1985.106