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- W2531385822 abstract "Aceclofenac has been used widely as a potent analgesic and anti-inflammatory drug. Aceclofenac is converted to 4'-hydroxyaceclofenac and diclofenac via CYP2C9-mediated hydroxylation and hydrolysis, respectively. CYP2C9 also mediates the hydroxylation of diclofenac to yield 4'-hydroxydiclofenac and the hydrolysis of 4'-hydroxyaceclofenac to 4'-hydroxydiclofenac. We aimed to model the metabolism of aceclofenac in volunteers using a compartmental modeling approach. After an oral dose of 100 mg aceclofenac in volunteers, plasma concentrations of aceclofenac and its three metabolites were measured. The pharmacokinetics of aceclofenac and the sequential formation of its three metabolites were analyzed using ADAPT 5. The delay parameter shifted the plasma aceclofenac concentration-time profile to the right and provided a large improvement of fit. Two compartments were needed to fit the aceclofenac and 4'-hydroxyaceclofenac data, and one additional compartment was sufficient to describe the time courses of the generated plasma concentrations of diclofenac and 4'-hydroxydiclofenac. The metabolism rate constant for 4'-hydroxyaceclofenac was much greater than that for diclofenac. The generation rate constant of 4'-hydroxydiclofenac from diclofenac was greater than that of its generation from 4'-hydroxyaceclofenac. Our model fully describes the time course of plasma aceclofenac concentration as well as the formation and disposition of its three major metabolites in volunteers." @default.
- W2531385822 created "2016-10-21" @default.
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- W2531385822 date "2016-12-01" @default.
- W2531385822 modified "2023-09-24" @default.
- W2531385822 title "Modeling of aceclofenac metabolism to major metabolites in healthy volunteers" @default.
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- W2531385822 doi "https://doi.org/10.1016/j.dmpk.2016.10.001" @default.
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