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  • Title: Studies on the influence of esterase inhibitor to the pharmacokinetic profiles of oseltamivir and oseltamivir carboxylate in rats using an improved LC/MS/MS method.
    Author: Chang Q, Chow MS, Zuo Z.
    Journal: Biomed Chromatogr; 2009 Aug; 23(8):852-7. PubMed ID: 19353695.
    Abstract:
    Oseltamivir (O), an ethyl ester prodrug of oseltamivir carboxylate (OC), is currently the drug of choice for avian influenza. Previous studies have found that the addition of esterase inhibitor can inhibit the metabolism of O to OC in plasma samples. The current study aims to evaluate the impact of dichlorvos on the rat plasma concentrations of O and OC and subsequent effect on their pharmacokinetics. The plasma samples of rats after oral administration of O were divided into two equal portions for treatment with/without dichlorvos. O and OC plasma concentrations were analyzed by a sensitive and specific LC/MS/MS method, using cephalexin as internal standard for both two analytes. The samples were extracted with an MCX cartridge and separated on a Nova-Pak CN HP column eluted with a mobile phase of 0.15% formic acid in 50% methanol. The results showed that dichlorvos significantly inhibited further hydrolysis of O to OC during the period of rat plasma sample treatment. A significant difference in the pharmacokinetic parameters of O (except for T(max) and t(1/2,lambdaz)) was found when the plasma samples were treated with dichlorvos. The use of dichlorvos is recommended in all rat studies which require plasma concentration determination of O and OC.
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