Inter- and intra-subject variability in ethanol pharmacokinetic parameters: effects of testing interval and dose.
Calculation of a blood alcohol concentration (BAC) at the time of an offence by forward or back-extrapolation, using population average values for ethanol pharmacokinetic parameters or a single estimate of individual specific parameters, ignores the possibility of inter- and intra-subject variability. In order to estimate inter- and intra-subject variability in the elimination rate and absorption rate, BAC was measured over time in 12 male volunteers on 4 occasions. Subjects received 0.44 g kg(-1) body weight of ethanol on the first study day, and 0.70 g kg(-1) body weight on subsequent study days 1, 11 and 12 weeks later, to enable comparisons in variability over short and long time periods and when the same or different doses were administered. Evidence of both inter- and intra-subject variability was found, with inter-subject variability substantially smaller than intra-subject variability when the dose varied. Forensically important differences in pharmacokinetic parameters were observed within individuals between occasions. These findings could have an important impact on medico-legal issues related to ethanol pharmacokinetics.
Yelland
Lisa N
LN
Discipline of Public Health, School of Population Health and Clinical Practice, The University of Adelaide, Adelaide 5005, Australia. lisa.yelland@adelaide.edu.au
Burns
Jaimi P
JP
Sims
D Noel
DN
Salter
Amy B
AB
White
Jason M
JM
D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000331:legislation & jurisprudence; D001334:Automobile Driving / Q000331:legislation & jurisprudence; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D053593:Forensic Toxicology; D006801:Humans; D016014:Linear Models; D008297:Male
D002492:Central Nervous System Depressants; D000431:Ethanol