Cimetidine increases steady state plasma levels of propranolol.

Abstract

1 The influence of cimetidine (1000 mg daily) on propranolol steady state plasma levels has been studied in seven normal volunteers. Cimetidine was used as a 200 mg normal release tablet whereas propranolol was given as a 160 mg slow release formulation once daily. 2 After 1 day of cimetidine treatment (day 9 of the study) the mean (Css) and minimal (Css min) propranolol steady state plasma levels increased significantly from 24.1 +/‐ 14.9 ng/ml (mean +/‐ s.d.) to 39.2 +/‐ 27.7 ng/ml (P = 0.01) and from 14.8 +/‐ 9.3 ng/ml to 27.1 +/‐ 21.2 ng/ml (P = 0.03), respectively. The apparent oral clearance (Clo) was reduced from 6.7 +/‐ 4.3 l/min to 4.6 +/‐ 3.11/min (P = 0.006). 3 A prolongation of cimetidine administration to 5 days (day 13 of the study) intensified this effect significantly (P = 0.02): Css of propranolol was elevated from 23.2 +/‐ 14.4 ng/ml to 44.9 +/‐ 26.7 ng/ml (P = 0.003); Css min was increased from 14.1 +/‐ 10.2 ng/ml to 28.4 +/‐ 17.9 ng/ml (P = 0.02) while Clo decreased from 6.9 +/‐ 4.1 1/min to 3.3 +/‐ 1.61/min (P = 0.006). 4 We conclude that the drug interaction between propranolol and cimetidine leads to significant elevations of propranolol steady state plasma concentrations which may cause a clinically relevant enhancement of the effect of a given dosage. This requires careful observation of patients under concomitant treatment with propranolol and cimetidine. 1981 The British Pharmacological Society