Disposition and bioavailability of the β1‐adrenoceptor antagonist talinolol in man

Abstract

In an open randomized crossover study, the pharmacokinetics and bioavailability of the selective β₁‐adrenoceptor antagonist talinolol (Cordanum®—Arzneimittelwerk Dresden GmbH, Germany) were investigated in twelve healthy volunteers (five female, seven male; three poor and nine extensive metabolizers of the debrisoquine hydroxylation phenotype) 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 ± 95 ng mL⁻¹ (mean ± SD) was observed. The area under the serum concentration‐time curve from zero to infinity (AUC_0‐∞) was 1433 ± 153 ng h mL⁻¹. The following 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 distribution, 3.3 ± 0.5 L kg⁻¹; and total body clearance, 4.9 ± 0.6 mL min⁻¹ kg⁻¹. Within 36 h 52.8 ± 10.6% of the administered dose was recovered 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 ± 0.8h. The AUC_0‐∞ 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 unchanged 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 incomplete absorption. Talinolol disposition is not found to be altered in poor metabolizers of debrisoquine type.