Pharmacokinetics of calcium blockers in patients with renal insufficiency and in geriatric patients

Abstract

Calcium antagonists have been used in the treatment of various medical disorders for more than 10 years, but their pharmacokinetics properties are poorly investigated. Available data on the pharmacokinetics of calcium antagonists in normal men are summarized in the present paper. Information on the influence of renal impairment and old age on the handling of calcium-antagonists are only available for verapamil. Patients with advanced renal disease had a significant reduction in the apparent volume of distribution, a shortened serum elimination half life, a decreased total body clearance of verapamil due to a decrease in the renal excretion of verapamil and its active metabolite norverapamil and also to a decrease in metabolic clearance. Pharmacokinetic parameters obtained after oral administration were not significantly different from those after intravenous dosing. The mean biologic availability (22.8%) was in the same range as reported for normal persons, but individual variations would seem to be greater. Elderly patients with a mean age of 87 years also had a significantly reduced volume of distribution of verapamil and decreased total body clearance of the drug, although this last change did not reach statistical significance. The biologic availability in the elderly was higher than in younger persons with a mean value of 37.69% and a wide range from 9.16 to 82.76%. These findings imply that verapamil dosage should be reduced in patients with impaired renal function and elderly patients.