The disposition of the beta-blocking
drug talinolol is controlled by
P-glycoprotein in man. Because
talinolol is marketed as a racemate, we reevaluated the serum-concentration time profiles of
talinolol of a previously published study with single intravenous (30 mg) and repeated oral
talinolol (100 mg for 14 days) before and after comedication of
rifampicin (600 mg per day for 9 days) in eight male healthy volunteers (age 22-26 years,
body weight 67-84 kg) with respect to differences in the kinetic profiles of the two enantiomers S(-)
talinolol and R(+)
talinolol. Additionally, the metabolism of
talinolol in human liver microsomes was examined. After
oral administration, S(-)
talinolol was slightly less absorbed and faster eliminated than R(+)
talinolol. The absolute bioavailabilty of the R(+) enantiomer of
talinolol was slightly but significantly higher than of its S(-) enantiomer. Coadministration of
rifampicin further intensified this difference in the disposition of R(+) and S(-)
talinolol (p < 0.05). Formation of 4-trans hydroxytalinolol was the major metabolic pathway in human liver microsomes. All Cl(int) values of S(-) were higher than of R(+)
talinolol; 0.1 microM
ketoconazole inhibited the formation of all metabolites. In conclusion, the stereoselectivity of
talinolol disposition is of minor importance, and most likely caused by presystemic biotransformation via
CYP3A4. The less active R(+)
talinolol might be suitable for phenotyping
P-glycoprotein expression in man.