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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antiviral Agents / administration & dosage
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Antiviral Agents / pharmacokinetics
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Area Under Curve
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Carboxylic Ester Hydrolases* / genetics
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Carboxylic Ester Hydrolases* / metabolism
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Dose-Response Relationship, Drug
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Drug Monitoring
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Female
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Genotype
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Humans
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Influenza A virus / drug effects*
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Influenza B virus / drug effects*
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Influenza, Human / drug therapy*
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Male
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Oseltamivir* / administration & dosage
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Oseltamivir* / analogs & derivatives
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Oseltamivir* / pharmacokinetics
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Polymorphism, Genetic
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Prodrugs / administration & dosage
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Prodrugs / pharmacokinetics
Substances
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Antiviral Agents
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Prodrugs
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Oseltamivir
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Carboxylic Ester Hydrolases
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CES1 protein, human
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oseltamivir carboxylate