alexa Metabolite formation pharmacokinetics: rate and extent of metabolite formation determined by deconvolution.


Journal of Drug Metabolism & Toxicology

Author(s): Karol MD, Goodrich S

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Abstract A two-step analytic procedure to determine the rate and extent of metabolite production following administration of the parent compound is described. The procedure provides the rate and extent of metabolite production as a function of time by application of the general model independent approach of deconvolution. The metabolite unit impulse response function is obtained by implicit deconvolution of the metabolite data with a truncated constant-rate metabolite input function. Then the obtained unit impulse response function is used in an analytic deconvolution with metabolite data following administration of the parent compound to obtain the rate and extent of metabolite production. The input function is also deconvolved with metabolite data to obtain the unit impulse response function appropriate for prediction of metabolite levels given a selected input of parent compound. The expected profile following administration of the consecutive infusions of parent drug is shown for both parent and metabolite. The rationale for selection of deconvolution methods is discussed. The approach is applied to data for procainamide and N-acetylprocainamide from three human subjects. The results indicate that from 27 to 39\% of the procainamide was converted to N-acetylprocainamide in these subjects.
This article was published in Pharm Res and referenced in Journal of Drug Metabolism & Toxicology

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