Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/23911
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dc.contributor.authorNg, Wenzie-
dc.contributor.authorUchida, Hiroyuki-
dc.contributor.authorIsmail, Zahinoor-
dc.contributor.authorMamo, David-
dc.contributor.authorRajji, Tarek K.-
dc.contributor.authorRemington, Gary-
dc.contributor.authorSproule, Beth A.-
dc.contributor.authorPollock, Bruce G.-
dc.contributor.authorMulsant, Benoit H.-
dc.contributor.authorBies, Robert R.-
dc.date.accessioned2017-11-16T10:15:06Z-
dc.date.available2017-11-16T10:15:06Z-
dc.date.issued2009-
dc.identifier.citationNg, W., Uchida, H., Ismail, Z., Mamo, D. C., Rajji, T. K., Remington, G., ... & Bies, R. R. (2009). Clozapine exposure and the impact of smoking and gender: a population pharmacokinetic study. Therapeutic Drug Monitoring, 31(3), 360-366.en_GB
dc.identifier.urihttps://www.um.edu.mt/library/oar//handle/123456789/23911-
dc.description.abstractThe primary objective of this study was to evaluate the magnitude and variability of concentration exposure to clozapine and norclozapine in a real-world clinical setting, with a focus on smoking status, using population pharmacokinetic methodologies. A retrospective review of plasma clozapine and norclozapine concentrations taken from inpatients at the Centre for Addiction and Mental Health, Toronto, from 2001 to 2007 was conducted. A nonlinear mixed-effects model was developed using NONMEM, including age, gender, weight, smoking status, and dosage formulation as covariates. Pharmacokinetic parameters and interindividual and residual variabilities were estimated with 1- and 2-compartment models. A total of 519 plasma clozapine concentrations from 197 patients (138 males; mean ± SD age, 38 ± 13 years; schizophrenia spectrum disorder 98.2%) were included for the analysis. A 1-compartment model with first-order absorption and elimination best described the data. Apparent volume of distribution was fixed to a previously reported value in the literature of 7 L/kg. The population-predicted oral clearance of clozapine and norclozapine was 18.0 and 39.0 L/h, respectively; both the predicted clearance values vary nearly 6-fold (range, 9.18-59.06 and 16.29-97.84 L/h, respectively). For clozapine, smokers and males showed increased oral clearance by 6.0 and 4.5 L/h, respectively. For norclozapine, smokers and male gender were associated with an increased oral clearance of 11.3 and 7.6 L/h, respectively. The formulation of clozapine administered had an impact on the absorption rate with a Ka of 0.14/h for tablet and 10.3/h for the suspension form. The data suggest that smoking and male gender are associated with lower exposure to clozapine and norclozapine due to the higher oral clearance. These findings may account for some of the variability in clozapine exposure and have important implications for individualized drug dosing and therapeutic drug monitoring.en_GB
dc.language.isoenen_GB
dc.publisherLippincott Williams & Wilkinsen_GB
dc.rightsinfo:eu-repo/semantics/restrictedAccessen_GB
dc.subjectClozapineen_GB
dc.subjectNonlinear operatorsen_GB
dc.subjectPharmacokineticsen_GB
dc.subjectSmoking -- Health aspectsen_GB
dc.titleClozapine exposure and the impact of smoking and gender : a population pharmacokinetic studyen_GB
dc.typearticleen_GB
dc.rights.holderThe copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holderen_GB
dc.description.reviewedpeer-revieweden_GB
dc.identifier.doi10.1097/FTD.0b013e31819c7037-
dc.publication.titleTherapeutic Drug Monitoringen_GB
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