title: 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.
authors.affiliation: College of Pharmacy, University of Kentucky, Lexington 40536-0082.
authors.forename: D A
authors.initials: DA
authors.lastname: Smith
authors.forename: M H
authors.initials: MH
authors.lastname: Chandler
authors.forename: S I
authors.initials: SI
authors.lastname: Shedlofsky
authors.forename: P J
authors.initials: PJ
authors.lastname: Wedlund
authors.forename: R A
authors.initials: RA
authors.lastname: Blouin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D006591:Hexobarbital / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D012293:Rifampin / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D006591:Hexobarbital; D012293:Rifampin