URINARY-EXCRETION AND METABOLISM OF TERTATOLOL ENANTIOMERS AFTER ORAL-ADMINISTRATION OF THE RACEMATE TO MALE-VOLUNTEERS

The objective of this study was to investigate the presence of stereoselective processes in the pharmacokinetics and metabolism of tertatolol in humans, using urinary excretion data. Six healthy male volunteers were given single 5mg oral doses of (+,-)-tertatolol; the stereoisomers of tertatolol and its hydroxylated and glucuronidated metabolites in urine were determined by high-pressure liquid chromatography (HPLC). (-)-Tertatolol was found in higher amounts in urine compared with the other enantiomer, with a (-)/(+) ratio of 1.45. The (-)/(+) ratio of 0.39 for the glucuronic acid conjugates of tertatolol enantiomers suggested a high stereoselectivity in glucuronidation. However, the glucuronidation of 4-hydroxytertatolo did not exhibit any stereoselectivity. A high product stereoselectivity in the formation of 3-hydroxytertatolol was found for (+)-tertatolol but not for (-)-tertatolol. The ratio of the two stereoisomers originating from (+)-tertatolol being equal to 2.2. These observations, based solely on urine data, strongly suggest the presence of stereoselectivity in tertatolol pharmacokinetics and metabolism in humans. However, more specific studies are necessary to determine which are the stereoselective processes and to evaluate the clinical implications of these observations.