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  • Title: Pharmacokinetic model for diazepam and its major metabolite desmethyldiazepam following diazepam administration.
    Author: Jack ML, Colburn WA.
    Journal: J Pharm Sci; 1983 Nov; 72(11):1318-23. PubMed ID: 6417322.
    Abstract:
    A five-compartment open model was used to simulate the blood concentration profiles of diazepam and its metabolite, desmethyldiazepam, following single- and multiple-dose administrations of diazepam. The parameter estimates for diazepam were previously reported literature values. The parameters estimates for the metabolite were calculated from literature values of blood concentrations of desmethyldiazepam following the administration of clorazepate. The five-compartment open model suggests that approximately 50% of the administered diazepam is biotransformed to desmethyldiazepam, and that the elimination profile of the metabolite is not altered by the presence of the drug. The model may also be readily adapted to predict the concentrations of diazepam and desmethyldiazepam in cerebrospinal fluid following the administration of diazepam by simply correcting the blood or plasma concentrations of the drug and metabolite for the degree of plasma protein binding.
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