Objective: This study aimed to evaluate the influence of cigarette smoking habit on the clozapine (CLZ)-to-norclozapine (norCLZ) ratio in male patients.
Methods: The sample consisted of plasma concentration of CLZ and norCLZ data set. The mean values of CLZ, norCLZ, and CLZ-to-norCLZ, between male patients who smoke versus nonsmokers were compared.
Findings: CLZ mean plasma level of 142 ± 80 ng/ml and 305 ± 159 ng/ml, norCLZ mean plasma level of 93 ± 72 ng/ml and 234 ± 62 ng/ml, and mean CLZ-to-norCLZ plasma level ratio of 2.1 ± 1.1 and 1.5 ± 0.5, were obtained respectively for male patients who smoke and nonsmokers.
Conclusion: This study has shown a significant decrease in CLZ and norCLZ plasma levels, and an increase in the CLZ-to-norCLZ ratio, in smokers as compared to nonsmokers, due to an increase in the clearance of CLZ and norCLZ by smoking induction of CYP 1A2 and glucuronidation by uridyl glucuronyl transferase enzymes (UGT), mainly UGT 1A4, respectively, as the most probable cause.
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http://dx.doi.org/10.4103/jrpp.jrpp_37_23 | DOI Listing |
J Res Pharm Pract
November 2023
Unit for the Rational Use of Medicines, Aragon Health Service, Zaragoza, Spain.
Objective: This study aimed to evaluate the influence of cigarette smoking habit on the clozapine (CLZ)-to-norclozapine (norCLZ) ratio in male patients.
Methods: The sample consisted of plasma concentration of CLZ and norCLZ data set. The mean values of CLZ, norCLZ, and CLZ-to-norCLZ, between male patients who smoke versus nonsmokers were compared.
Eur Arch Psychiatry Clin Neurosci
February 2024
Department of Psychiatry and Neurosciences, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
Obsessive-compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clozapine (CLZ). This study aimed to analyze prevalence of OCS and obsessive-compulsive disorder (OCD) in this subgroup and find possible correlations with different phenotypes. Additionally, this is the first study to examine polygenetic risk scores (PRS) in individuals with SCZ and OCS.
View Article and Find Full Text PDFBasic Clin Pharmacol Toxicol
April 2018
Centre for Pharmacology and Therapeutics, Imperial College London, London, UK.
The atypical antipsychotic agent clozapine (CLZ) is effective in many patients who are resistant to conventional antipsychotic drugs. Cytochromes P450 (CYPs) 1A2 and 3A4 oxidize CLZ to norCLZ and CLZ N-oxide in human liver. Concurrent treatment with inducers and inhibitors of CYP1A2 modulates CLZ elimination that disrupts therapy.
View Article and Find Full Text PDFJ Pharmacol Sci
October 2014
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, China.
Clozapine (CLZ) was reported to be associated with hepatotoxicity. Glycyrrhetinic acid (GA) has a liver protective effect. Our preliminary experiments showed that GA aggravated rather than attenuated CLZ-induced hepatotoxicity in primary cultured rat hepatocytes.
View Article and Find Full Text PDFDrug Metab Dispos
December 2008
Pharmacogenomics and Drug Development Group, University of Sydney, NSW 2006, Australia.
The atypical antipsychotic drug clozapine (CLZ) is effective in a substantial number of patients who exhibit treatment-resistance to conventional agents. CYP1A2 is generally considered to be the major enzyme involved in the biotransformation of CLZ to its N-demethylated (norCLZ) and N-oxygenated (CLZ N-oxide) metabolites in liver, but several studies have also implicated CYP3A4. The present study assessed the interplay between these cytochrome P450s (P450s) in CLZ biotransformation in a panel of hepatic microsomal fractions from 14 individuals.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!