| Autor: |
Katz, David A., Locke, Charles, Liu, Wei, Zhang, Jun, Achari, Ramanuj, Wesnes, Keith A., Tracy, Katherine A. |
| Zdroj: |
Alcoholism: Clinical and Experimental Research; April 2016, Vol. 40 Issue: 4 p838-845, 8p |
| Abstrakt: |
ABT‐436, a potent and selective arginine vasopressin (AVP) type 1Breceptor (V1B) antagonist, has previously demonstrated basal hypothalamic–pituitary–adrenal (HPA) axis attenuation in man. A V1Bantagonist is hypothesized as an alcohol‐dependent treatment based on the role of the V1Breceptor in stress regulation and the finding that stress is a trigger for relapse in alcoholics. A V1Bantagonist 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. 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. 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 HPAaxis. No pharmacokinetic or pharmacodynamic interaction between ABT‐436 and alcohol was observed. Arginine vasopressin type 1B (V1B) receptor antagonists have potential for treatment of alcohol dependence based on the receptor's role in stress regulation. ABT‐436, a potent and selective V1B antagonist, decreases HPAaxis activity in man and is being investigated in a NIAAA‐sponsored clinical trial in alcohol‐dependent patients. In a single‐dose drug–drug interaction clinical trial, Katz et al. provide evidence that ABT‐436 and alcohol each do not alter the pharmacokinetics or pharmacodynamics of the other. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Plný text