Effect of cimetidine on verapamil disposition

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Abstract
The effects of multiple doses of cimetidine on single-dose verapamil kinetics were studied in 9 healthy men. Baseline hepatic blood flow was estimated by indocyanine green elimination on day 1. One 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 4 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 t1/2 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. Cimetidine apparently reduces verapamil clearance by mechanism(s) other than a change in hepatic blood flow or volume of distribution.