DISPOSITION AND BIOAVAILABILITY OF THE BETA(1)-ADRENOCEPTOR ANTAGONIST TALINOLOL IN MAN

In an open randomized crossover study, the pharmacokinetics and bioava ilability of the selective beta(1)-adrenoceptor antagonist talinolol ( Cordanum(R) - Arzneimittelwerk Dresden GmbH, Germany) were investigate d in twelve healthy volunteers (five female, seven male; three poor an d nine extensive metabolizers of the debrisoquine hydroxylation phenot ype) after intravenous infusion (30 mg) and oral administration (50 mg ), respectively. Concentrations of talinolol and its metabolites were measured in serum and urine by HPLC or GC-MS. At the end of infusion a peak serum concentration (C-max) of 631+/-96 ng mL(-1) (mean +/- SD) was observed. The area under the serum concentration-time curve from z ero to infinity (AUC(0-infinity)) was 1433+/-153 ng h mL(-1). The foll owing parameters were estimated: terminal elimination half life (t(1/2 )), 10.6+/-3.3 h; mean residence time, 11.6+/-3.1 h; volume of distrib ution, 3.3+/-0.5 L kg(-1); and total body clearance, 4.9+/-0.6 mL min( -1) kg(-1) within 36h 52.8+/-10.6% of the administered dose was recove red as unchanged talinolol and 0.33+/-0.18% as hydroxylated talinolol metabolites in urine. After oral administration a C-max of 168+/-67 ng mL(-1) was reached after 3.2+/-0.8 h. The AUC(0-infinity) was 1321+/- 382 ng h mL(-1). The t(1/2) was 11.9+/-2.4 h. 28.1+/-6.8% of the dose or 55.0+/-11.0% of the bioavailable talinolol was eliminated as unchan ged talinolol and 0.26+/-0.17% of the dose as hydroxylated metabolites by kidney. The absolute bioavailability of talinolol was 55+/-15% (95 % confidence interval, 36-69%). Talinolol does not undergo a relevant first-pass metabolism, and its reduced bioavailability results from in complete absorption. Talinolol disposition is not found to be altered in poor metabolizers of debrisoquine type.