Effects of cimetidine and ranitidine on steady-state propranolol kinetics and dynamics

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Abstract
The influence of cimetidine (1000 mg daily, 1 day oral pretreatment) and ranitidine (300 mg daily by mouth, 1 and 6 days pretreatment) on steady-state propranolol (160 mg sustained-release capsule, once daily) plasma levels (Psss) and dynamic .beta.-blocker effects was assessed by bicycle ergometer exercise and isoproterenol sensitivity test in 5 normal subjects. During the 3 h of the dynamic tests Psss were elevated from 25% to 67% by cimetidine, whereas Pss was unchanged by ranitidine. The estimated hepatic blood flow (EHBF) as calculated from indocyanine green (ICG) plasma clearance was only slightly reduced by 15 .+-. 23% (mean .+-. SD, n [no.] = 4) after 1 oral dose of 150 mg ranitidine and showed substantial intersubject variability. Dynamic parameters, like propranolol-induced heart rate and blood pressure changes under physical exercise or during the isoproterenol sensitivity test, were not influenced by ranitidine or cimetidine. Since this study was performed on normal subjects with relatively low propranolol doses these results do not rule out the risk of severe reinforcement of .beta.-adrenergic receptor blocking effects if propranolol and cimetidine are taken together by patients. [Cimetidine and ranitidine, histamine H2-receptor antagonists, are usually used for prolonged periods in gastrointestinal ulcer disease. Their interference with other drugs also given over the long term could lead to negative interactions.].