¹Virginia Commonwealth University, National Institute on Alcohol Abuse and Alcoholism, Richmond, VA, USA

Abstract

AT is defined as a decrease in effect with prolonged exposure during the time course of a single dose. Development of AT to the perception of intoxication has been reported after ETH administration in young persons. Since the elderly have less CNS reserve, it is hypothesized that they will not develop AT to the same degree as the young. This study was designed to evaluate AT development in the elderly. Eight men (mean age 72.4 yr; range 70-82 yr) and 7 women (mean age 74.9 yr; range 69-88 yr) underwent pharmacokinetic (PK) screening to determine individual PK characteristics and estimate ETH doses to achieve and sustain serum ETH concentrations (SEC) at a target of 1000 mg/L. Later, they received a 1-hr IV ETH infusion to achieve target SEC, followed by a 5-hr IV ETH infusion to maintain target SEC. SEC was measured by TDx/TDxFlx. The pharmacodynamic (PD) effect was measured by a subject-rated impairment (SRI) scale and number vigilance speed (NVS). The degree of AT was estimated using PK-PD modeling. Vd_ss was lower in the elderly (males 0.38 L/kg; females 0.36 L/kg) than reported for the young, supporting earlier findings. AT to SRI was noted in only 4 of 15 elderly compared to 14 of 16 young volunteers studied in the same laboratory. NVS showed no AT; sensitivity was similar to the young, but baseline performance was lower in the elderly. The elderly appear to develop AT to the subjective effects of ETH to a lesser degree/at a slower rate than the young.