Carboxylesterase 1 Polymorphism Impairs Oseltamivir Bioactivation in Humans

Abstract

Bioactivation of the antiviral agent oseltamivir to active oseltamivir carboxylate is catalyzed by carboxylesterase 1 (CES1). After the screening of 860 healthy Finnish volunteers for the CES1 c.428G>A (p. Gly143Glu, rs121912777) polymorphism, a pharmacokinetic study with 75 mg oseltamivir was carried out in c.428G>A carriers and noncarriers. Heterozygous c.428GA carriers (n = 9) had 18% larger values of oseltamivir area under the plasma concentration–time curve from 0 h to infinity (AUC_0–∞) (P = 0.025) and 23% smaller carboxylate‐to‐oseltamivir AUC_0–∞ ratio (P = 0.006) than noncarriers (n = 12). This shows that the CES1 c.428G>A polymorphism impairs oseltamivir bioactivation in humans. Clinical Pharmacology & Therapeutics (2012); 92 1, 68–71. doi:10.1038/clpt.2012.13