Since calcium channel antagonists are a diverse class of drugs frequently administered in combination with other agents, the potential for clinically significant pharmacokinetic drug interactions exists. These interactions occur most frequently via altered hepatic blood flow and impaired hepatic enzyme activity. Part I of the article, which appeared in the previous issue of the Journal, dealt with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs. Part II examines interactions with cyclosporin, anaesthetics, carbamazepine and cardiovascular agents.

Calcium channel antagonists are a diverse class of drugs widely used in combination with other therapeutic agents. The potential exists for many clinically significant pharmacokinetic interactions between these and other concurrently administered drugs. The mechanisms of calcium channel antagonist-induced changes in drug metabolism include altered hepatic blood flow and impaired hepatic enzyme metabolising activity. Increases in serum concentrations and/or reductions in clearance have been reported for several drugs used with a number of calcium channel antagonists. A number of reports and studies of calcium channel antagonist interactions have yielded contradictory results and the clinical significance of pharmacokinetic changes seen with these agents is ill-defined. The first part of this article deals with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs.

Penbutolol is a new beta-adrenergic blocking drug approved for the treatment of hypertension. It is a noncardioselective beta-blocker and has intrinsic sympathomimetic activity. The drug is approximately four times as potent as propranolol when taken orally. After oral administration, it is almost completely absorbed and peak plasma concentrations are achieved within 1.0 to 2.25 hours. Penbutolol is extensively metabolized in the liver by hydroxylation and glucuronidation. Active metabolites have not been identified. Only four to six percent of the parent drug is eliminated in the urine unchanged and dosage adjustment in renal insufficiency does not appear to be necessary. The mean terminal half-life of penbutolol is 17.6 to 26.5 hours. The duration of the hypotensive effect is approximately 24 hours. Current dosing guidelines recommend initiating therapy with 20 mg/d administered once a day. Optimum hypotensive effect occurs at dosages of 20-40 mg/d with little additional benefit observed above this range. Penbutolol appears to be well tolerated. The adverse effect profile is similar to other beta-blockers.