{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T13:41:29Z","timestamp":1758634889560},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,1,12]],"date-time":"2015-01-12T00:00:00Z","timestamp":1421020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label \/><jats:p>The aim of this study was to evaluate whether genetic polymorphisms in <jats:italic>CYP3A5<\/jats:italic> and <jats:italic>ABCB1<\/jats:italic> are responsible for the interindividual variability observed in quetiapine pharmacokinetics. Pharmacokinetic data from a randomized crossover study evaluating 2 quetiapine 25\u2009mg immediate\u2010release tablets after single oral dose were used to develop a population pharmacokinetic model. The single nucleotide polymorphisms (SNPs) evaluated for the genotype effects of quetiapine pharmacokinetics were <jats:italic>CYP3A5<\/jats:italic> A6986G and <jats:italic>ABCB1<\/jats:italic> C3435T, along with other demographic variables and formulations. A one\u2010compartment distribution model with linear elimination plus four transit compartments for the delayed absorption adequately described quetiapine disposition. <jats:italic>CYP3A5<\/jats:italic> *1\/*1 individuals (n\u2009=\u20093) had 29% increased clearance compared to *1\/*3 and *3\/*3 individuals. The impact of an increased clearance was evaluated by simulations. By computing the probability of target attainment (PTA) of steady\u2010state therapeutic goal at 1\u2010hour and 12\u2010hour time points after 50\u2013400\u2009mg twice\u2010daily regimens, the results indicated that <jats:italic>CYP3A5<\/jats:italic> genotype has minimal impact on the PTA of the 1\u2010hour concentrations but a significant impact on the 12\u2010hour concentrations. The interpretation based on the simulations does not call for a genotype\u2010based dosing scheme and is consistent with consensus guidelines for quetiapine that therapeutic drug monitoring is considered useful. 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