A comparative study of two methods for attaining constant alcohol levels.
OBJECTIVE
Alcohol effects or drug-alcohol interactions are preferably studied at constant blood levels. To achieve pseudo-steady state levels, various methods are used, which usually produce adequate averages but variable individual concentration profiles. The aim was to compare two modes of alcohol administration: a 'two-step prekinetic procedure' and a 'clamping method'.


METHODS
The two-step prekinetic procedure started with determination of individual pharmacokinetic (PK) parameters, during a prestudy occasion. Individual infusion regimens were calculated afterwards, based on a pseudo-steady state breath alcohol concentration (BrAC) of 0.65 g l(-1) and applied on a separate occasion. For the clamping procedure, a spreadsheet-based paradigm was developed using BrAC-guided adjustments of infusion rates, to maintain stable BrAC levels of 0.6 g l(-1).


RESULTS
The mean BrAC during clamping [0.61 g l(-1), 95% confidence interval (CI) 0.58, 0.63] did not differ from its intended level of 0.6 g l(-1) (1.0% on average). In contrast, the mean BrAC during the prekinetic procedure was significantly lower than the 0.65 g l(-1) set-point (0.59 g l(-1), 95% CI 0.54, 0.63) and deviated from this target by 9.7% on average. The clamping method also showed less variation between subjects [coefficient of variation (CV) 6.2%] compared with the prekinetic procedure (CV 14.6%).


CONCLUSIONS
Although the two methods differ considerably in their approach, clamping of BrAC resulted in more accurate alcohol levels than infusion based on PK modelling and does not require an extra prestudy occasion. The novel alcohol clamping paradigm can be of value in future studies of alcohol interactions or the pharmacodynamics of acute alcohol administration.
Zoethout
Remco W M
RW
Centre for Human Drug Research, Department of Anaesthesiology, Leiden, the Netherlands. rzoethout@chdr.nl
van Gerven
Joop M A
JM
Dumont
Glenn J H
GJ
Paltansing
Sunita
S
van Burgel
Nathalie D
ND
van der Linden
Monique
M
Dahan
Albert
A
Cohen
Adam F
AF
Schoemaker
Rik C
RC
D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000097:blood; D000435:Alcoholic Intoxication / Q000097:blood; D001944:Breath Tests; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000431:Ethanol / Q000008:administration & dosage* / Q000032:analysis / Q000097:blood*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008956:Models, Chemical; D012107:Research Design; D055815:Young Adult
D000431:Ethanol