The pharmacokinetics of a controlled-release formulation (coat-core) of the calcium channel blocker nisoldipine was investigated in eight subjects with biopsy-proved liver cirrhosis and eight healthy subjects. In Stage I, subjects received a single 10-mg dose to determine if this dose would be safely tolerated in the subjects with cirrhosis. Because all subjects in both groups tolerated the dose without difficulty, all were continued to Stage II. In Stage II, subjects received a once-daily dose of 10-mg coat-core tablets for 7 days. Serial plasma samples were assayed for nisoldipine in both stages. The Cmaxand AUC of nisoldipine were approximately fourfold to fivefold higher (p < 0.01) in subjects with cirrhosis as compared to healthy subjects; however, there was overlap in the range of pharmacokinetic parameters between the two groups. The accumulation factor following multiple dosing was similar in both groups. Results suggest that nisoldipine dose should be optimized by monitoring of a pharmacodynamic end point, such as effect on blood pressure. It is likely that dose requirements for patients with liver disease will be lower.