Premium
Single‐Dose Interaction Study of the Arginine Vasopressin Type 1 B Receptor Antagonist ABT ‐436 and Alcohol in Moderate Alcohol Drinkers
Author(s) -
Katz David A.,
Locke Charles,
Liu Wei,
Zhang Jun,
Achari Ramanuj,
Wesnes Keith A.,
Tracy Katherine A.
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12996
Subject(s) - placebo , antagonist , vasopressin , crossover study , pharmacodynamics , alcohol , pharmacokinetics , pharmacology , medicine , endocrinology , receptor antagonist , chemistry , receptor , biochemistry , alternative medicine , pathology
Background ABT ‐436, a potent and selective arginine vasopressin ( AVP ) type 1 B receptor ( V 1B ) antagonist, has previously demonstrated basal hypothalamic–pituitary–adrenal ( HPA ) axis attenuation in man. A V 1B antagonist is hypothesized as an alcohol‐dependent treatment based on the role of the V 1B receptor in stress regulation and the finding that stress is a trigger for relapse in alcoholics. A V 1B 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 S ystem), B ond– L ader 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 S ystem 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.