The effect of age and liver disease on the pharmacokinetics of the calcium antagonist, nisoldipine

Abstract

Two studies were performed-one in elderly, hypertensive patients and one in patients with chronic liver disease-to investigate the effect of age and liver disease upon the pharmacokinetics of nisoldipine, a dihydropyridine-type calcium antagonist. The effect of acute and chronic administration of nisoldipine (once and twice daily) was investigated in 17 elderly hypertensive patients. Compared with previously published data from young healthy volunteers, the values for Cmax and AUC appear to be higher in elderly hypertensive patients while Tmax and half-life were unchanged. Nisoldipine significantly reduced both systolic and diastolic blood pressure when given acutely to elderly hypertensive patients. Major alterations in the pharmacokinetics of nisoldipine were found in 7 patients with chronic liver disease when compared with the elderly hypertensives and healthy volunteers. The values for AUC, Cmax, half-life and volume of distribution were all higher than expected from the volunteer data while clearance was lower. One patient receiving primidone had very low nisoldipine levels, suggesting that the concomitant administration of agents that may induce the metabolism of nisoldipine should be discouraged. Nevertheless, comparisons of nisoldipine plasma levels after acute and chronic administration showed no evidence of any accumulation in either patient population in the doses used. The drug was generally well tolerated although 1 patient with chronic liver disease was withdrawn due to fluid retention.