Age‐dependent stereoselective increase in the oral clearance of hexobarbitone isomers caused by rifampicin.

Abstract

1. The disposition of hexobarbitone enantiomers before and after rifampicin treatment (600 mg daily for 14 days) was investigated in six young (29 +/- 3 years old) and six elderly (71 +/- 4 years old) healthy male volunteers. Hexobarbitone was given as a single 500 mg oral dose of the racemate. 2. The mean (+/- s.d.) oral clearance of S-(+) hexobarbitone was 1.9 +/- 0.3 and 1.8 +/- 0.2 ml min-1 kg-1, respectively, in young and elderly subjects and increased approximately six fold following 14 days of rifampicin treatment in both young (to 11.9 +/- 2.2 ml min-1 kg-1) and elderly (to 10.7 +/- 2.8 ml min-1 kg-1) subjects. 3. In contrast, rifampicin treatment produced a larger and a differential increase in the oral clearance of R-(-) hexobarbitone in young and elderly subjects; an 89 fold change in the young (15.6 +/- 16.4 to 1146.7 +/- 1478.0 ml min-1 kg-1) and a 19 fold change (10.3 +/- 3.0 to 199.9 +/- 98.1 ml min-1 kg-1) in the elderly.