R. B. Parker, Z. Hu, S. C. Laizure; University of Tennessee College of Pharmacy, Memphis, TN

BACKGROUND: Human carboxylesterase-1 (CES1) and -2 (CES2) enzymes are primarily expressed in the liver and intestine, respectively, where they mediate first-pass metabolism of a diverse group of commonly used drugs containing ester groups. Ethanol is a known CES1 inhibitor but its effects on CES2 in humans are unknown. In this study, we used aspirin (ASA) as a CES2 probe drug in humans to determine if ethanol inhibits ASA hydrolysis to the salicylic acid (SA) metabolite.
METHODS: In a randomized crossover trial, 18 healthy volunteers (9 male, 9 female) received 650 mg of non-enteric coated ASA alone and with ethanol 0.6 g/kg mixed with orange juice on separate study days. Serial blood samples were collected for analysis of ASA and SA plasma concentrations by LC-MS/MS and pharmacokinetic parameters were estimated using non-compartmental analysis.
RESULTS: Results summarized in the Table show that ethanol did not affect ASA or SA pharmacokinetics. The mean ethanol Cmax was 0.06 + 0.03 g/dl.
CONCLUSION: Our results show that ethanol does not inhibit the hydrolysis of aspirin in humans. Ethanol is unlikely to significantly affect CES2 activity and result in clinically significant drug interactions with substrate drugs.
ParametersASA aloneASA + EthanolP value
Cmax (μg/ml)3.48 (0.38)3.57 (0.55)NS
AUC0→inf (µg·h/mL)7.69 (0.25)8.33 (0.28)NS
t1/2 (h)0.53 (0.28)0.57 (0.46)NS
Cmax (μg/ml)29.9 (0.20)30.1 (0.31)NS
AUC0→inf (µg·h/mL)218 (0.41)238 (0.28)NS
t1/2 (h)3.6 (0.46)3.8 (0.44)NS

Data expressed as geometric means (geometric coefficients of variation). NS, not significant.