Pharmacokinetics of epanolol after acute and chronic oral dosing in elderly patients with stable angina pectoris.

Abstract

1. Epanolol is a novel anti-anginal agent which is a beta 1-adrenoceptor partial agonist exhibiting selective beta 1-adrenoceptor antagonist and selective beta 1-adrenoceptor agonist activity. It is mainly metabolised to conjugates prior to excretion in urine and it was of interest to determine if any accumulation occurred in elderly patients. 2. The pharmacokinetics of epanolol have been studied over 72 h after a single oral dose of 200 mg and then over 24 h after 12 consecutive daily oral doses in 13 elderly patients with stable angina pectoris. 3. The peak plasma concentrations (mean +/- s.d.) after the single dose (25.7 +/- 17.0 ng ml-1) were not significantly different (P = 0.35) from those at steady state (32.4 +/- 20.9 ng ml-1). There was wide inter-individual variation on both occasions. The time to peak did not alter significantly during the study with mean values of 1.5 and 1.2 h on acute and chronic dosing respectively. 4. Plasma concentrations declined biphasically with a mean terminal phase half-life of 17 h and 5 fold inter-individual variation. 5. The mean area under the curve to 24 h was not significantly different (P = 0.26) after the single dose (59.0 +/- 29.8 ng ml-1 h) from that at steady state (78.4 +/- 55.0 ng ml-1 h). There was also wide inter-individual variation in these values. 6. In conclusion, the lack of significant accumulation of epanolol indicates that no alteration of dose is necessary when using epanolol in elderly patients with normal renal and hepatic function.