Calcium Channel Antagonists: Part VI: Clinical Pharmacokinetics of First and Second-generation Agents

A survey of the pharmacokinetic properties of the three prototypical calcium antagonist agents shows that they have in common a very high rate of hepatic first-pass metabolism with, in the case of verapamil and diltiazem, the formation of an active metabolite that affects the dose during chronic therapy. Therefore, the major factor altering the pharmacokinetic properties and the dose of the drug required is the capacity of the liver to metabolize the drug, which in turn depends on the hepatic blood flow and the activity of the hepatic metabolizing systems. Hence liver disease, a low cardiac output, and coadministration of certain drugs inducing or inhibiting the hepatic enzymes, all indirectly affect the pharmacokinetic properties of the calcium antagonists. There are also other potential drug interactions of a kinetic or dynamic nature that may arise. In general, renal disease has little effect on the pharmacokinetics of calcium antagonists.