Effects of short-term abstinence on alcohol elimination rate: Sex differences and method comparisons using the intravenous alcohol clamp

BACKGROUND: Sex differences in the escalation of drinking after brief abstinence have been documented. The possibility that changes in alcohol metabolism may explain these differences has not been previously examined. We tested whether short-term abstinence alters the alcohol elimination rate (AER) across sex and compared three methods for its estimation. METHODS: Sixty-six adults (56% female) aged 21-35 years reporting moderate-to-heavy drinking completed two counterbalanced intravenous alcohol clamp sessions under two conditions: one during a period of usual drinking and one after two weeks of monitored abstinence. AER was quantified with three approaches: a manual steady-state method, a deterministic infusion rate profile-based curve-fitting algorithm, and an automated, model-based parameter identification procedure (PID). The effects of condition, method, and sex were examined using linear mixed-effects models, and agreement among methods was examined with concordance statistics. RESULTS: Short-term abstinence did not consistently change AER, overall or differently across sex. A significant abstinence effect (p = 0.01) was observed in females with the PID method only. Males exhibited higher AER than females across both conditions (p < 0.001). The PID method yielded lower alcohol elimination estimates than Manual (p < 0.001) and Deterministic AER approaches, whereas the manual and deterministic methods did not differ. CONCLUSIONS: Sex differences in alcohol consumption following short-term abstinence are likely not explained by changes in AER. When comparing methodologies, the selection of a methodology should be consistent within analyses and selected based on experimental design.