title: Single-Dose Interaction Study of the Arginine Vasopressin Type 1B Receptor Antagonist ABT-436 and Alcohol in Moderate Alcohol Drinkers.
abstract: BACKGROUND
  ABT-436, a potent and selective arginine vasopressin (AVP) type 1B receptor (V1B ) antagonist, has previously demonstrated basal hypothalamic-pituitary-adrenal (HPA) axis attenuation in man. A V1B antagonist is hypothesized as an alcohol-dependent treatment based on the role of the V1B receptor in stress regulation and the finding that stress is a trigger for relapse in alcoholics. A V1B antagonist has shown favorable effects in rat models of alcohol dependence. A single-dose clinical study was conducted to assess the potential for pharmacokinetic or pharmacodynamic interaction between ABT-436 and alcohol.
  
  
  METHODS
  Twenty moderate alcohol drinkers each received the 4 possible combinations of a single 1,000 mg ABT-436 dose (or matching placebo) and a single 0.5 g/kg alcohol dose (or placebo for alcohol) in a double-blind, randomized, 4-period crossover study. Plasma ABT-436 and blood alcohol levels were measured to assess pharmacokinetic interactions. A computerized cognitive test battery (CDR System), Bond-Lader Visual Analog Scales scales, and a postural stability test were used to measure the effects of alcohol and the potential interaction with ABT-436. The pharmacologic effect of ABT-436 was assessed by measuring serum cortisol.
  
  
  RESULTS
  Neither ABT-436 nor alcohol affected the blood levels of the other. Alcohol reduced performance on 2 of 5 CDR System composite variables (power of attention, p = 0.002; quality of secondary episodic memory, p < 0.001), and decreased postural stability (p = 0.043). ABT-436 did not exacerbate those deleterious effects. ABT-436 reduced serum cortisol (p < 0.001), and alcohol did not significantly diminish this expected effect on the HPA axis.
  
  
  CONCLUSIONS
  No pharmacokinetic or pharmacodynamic interaction between ABT-436 and alcohol was observed.
authors.affiliation: AbbVie Inc., North Chicago, Illinois.
authors.forename: David A
authors.initials: DA
authors.lastname: Katz
authors.affiliation: AbbVie Inc., North Chicago, Illinois.
authors.forename: Charles
authors.initials: C
authors.lastname: Locke
authors.affiliation: AbbVie Inc., North Chicago, Illinois.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: AbbVie Inc., North Chicago, Illinois.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: AbbVie Inc., North Chicago, Illinois.
authors.forename: Ramanuj
authors.initials: R
authors.lastname: Achari
authors.affiliation: Bracket , Goring-on-Thames, United Kingdom.|Department of Psychology , Northumbria University, Newcastle, United Kingdom.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wesnes
authors.affiliation: AbbVie Inc., North Chicago, Illinois.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Tracy
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000097:blood*; D065092:Antidiuretic Hormone Receptor Antagonists / Q000008:administration & dosage* / Q000097:blood*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017483:Receptors, Vasopressin / Q000502:physiology
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; D000431:Ethanol
keywords: Alcohol; Arginine Vasopressin Type 1B Receptor Antagonist; Clinical Trial; Drug-Drug Interaction; Pharmacodynamics