title: A comparative study of two methods for attaining constant alcohol levels.
abstract: 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.
authors.affiliation: Centre for Human Drug Research, Department of Anaesthesiology, Leiden, the Netherlands. rzoethout@chdr.nl
authors.forename: Remco W M
authors.initials: RW
authors.lastname: Zoethout
authors.forename: Joop M A
authors.initials: JM
authors.lastname: van Gerven
authors.forename: Glenn J H
authors.initials: GJ
authors.lastname: Dumont
authors.forename: Sunita
authors.initials: S
authors.lastname: Paltansing
authors.forename: Nathalie D
authors.initials: ND
authors.lastname: van Burgel
authors.forename: Monique
authors.initials: M
authors.lastname: van der Linden
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cohen
authors.forename: Rik C
authors.initials: RC
authors.lastname: Schoemaker
mesh_terms: 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
chemical_list: D000431:Ethanol