B. Trausch et al., DISPOSITION AND BIOAVAILABILITY OF THE BETA(1)-ADRENOCEPTOR ANTAGONIST TALINOLOL IN MAN, Biopharmaceutics & drug disposition, 16(5), 1995, pp. 403-414
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.