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Article: The differential effects of steady-state fluvoxamine on the pharmacokinetics of olanzapine and clozapine in healthy volunteers

TitleThe differential effects of steady-state fluvoxamine on the pharmacokinetics of olanzapine and clozapine in healthy volunteers
Authors
Issue Date2004
PublisherSage Science Press (US). The Journal's web site is located at http://www.sagepub.com/journal.aspx?pid=169
Citation
Journal Of Clinical Pharmacology, 2004, v. 44 n. 7, p. 785-792 How to Cite?
AbstractThe combination of atypical antipsychotics and selective serotonin reuptake inhibitors is an effective strategy in the treatment of certain psychiatric disorders. However, pharmacokinetic interactions between the two classes of drugs remain to be explored. The present study was designed to determine whether there were different effects of steady-state fluvoxamine on the pharmacokinetics of a single dose of olanzapine and clozapine in healthy male volunteers. One single dose of 10 mg olanzapine (n = 12) or clozapine (n = 9) was administered orally. Following a drug washout of at least 4 weeks, all subjects received fluvoxamine (100 mg/day) for 9 days, and one single dose of 10 mg olanzapine or clozapine was added on day 4. Plasma concentrations of olanzapine, clozapine, and N-desmethylclozapine were assayed at serial time points after the antipsychotics were given alone and when added to fluvoxamine. No bioequivalence was found in olanzapine alone and cotreatment with fluvoxamine for the mean peak plasma concentration (Cmax), the area under the concentration-time curve from time 0 to last sampling time point (AUC 0-t), and from time 0 to infinity (AUC0-∞). Under the cotreatment, Cmax of olanzapine was significantly elevated by 49%, with a 32% reduced time (tmax) to Cmax, whereas the Cmax and tmax of clozapine were unaltered. The cotreatment increased the AUC0-t and AUC0-∞ of olanzapine by 68% and 76%, respectively, greater than those of clozapine (40% and 41%). The presence of fluvoxamine also prolonged the elimination half-life (t 1/2) of olanzapine by 40% and, to a much greater extent, clozapine by 370% but reduced the total body clearance (CL/F) of clozapine (78%) more significantly than it did for olanzapine (42%). The apparent volume of distribution (Vd) was suppressed by 31% in olanzapine combined with fluvoxamine but was unaltered in the clozapine regimen. A significant reduction in the N-desmethylclozapine to clozapine ratio was present in the clozapine with fluvoxamine regimen. The effects of fluvoxamine on different aspects of pharmacokinetics of the two antipsychotics may have implications for clinical therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/179428
ISSN
2015 Impact Factor: 2.555
2015 SCImago Journal Rankings: 0.972
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWang, CYen_US
dc.contributor.authorZhang, ZJen_US
dc.contributor.authorLi, WBen_US
dc.contributor.authorZhai, YMen_US
dc.contributor.authorCai, ZJen_US
dc.contributor.authorWeng, YZen_US
dc.contributor.authorZhu, RHen_US
dc.contributor.authorZhao, JPen_US
dc.contributor.authorZhou, HHen_US
dc.date.accessioned2012-12-19T09:56:24Z-
dc.date.available2012-12-19T09:56:24Z-
dc.date.issued2004en_US
dc.identifier.citationJournal Of Clinical Pharmacology, 2004, v. 44 n. 7, p. 785-792en_US
dc.identifier.issn0091-2700en_US
dc.identifier.urihttp://hdl.handle.net/10722/179428-
dc.description.abstractThe combination of atypical antipsychotics and selective serotonin reuptake inhibitors is an effective strategy in the treatment of certain psychiatric disorders. However, pharmacokinetic interactions between the two classes of drugs remain to be explored. The present study was designed to determine whether there were different effects of steady-state fluvoxamine on the pharmacokinetics of a single dose of olanzapine and clozapine in healthy male volunteers. One single dose of 10 mg olanzapine (n = 12) or clozapine (n = 9) was administered orally. Following a drug washout of at least 4 weeks, all subjects received fluvoxamine (100 mg/day) for 9 days, and one single dose of 10 mg olanzapine or clozapine was added on day 4. Plasma concentrations of olanzapine, clozapine, and N-desmethylclozapine were assayed at serial time points after the antipsychotics were given alone and when added to fluvoxamine. No bioequivalence was found in olanzapine alone and cotreatment with fluvoxamine for the mean peak plasma concentration (Cmax), the area under the concentration-time curve from time 0 to last sampling time point (AUC 0-t), and from time 0 to infinity (AUC0-∞). Under the cotreatment, Cmax of olanzapine was significantly elevated by 49%, with a 32% reduced time (tmax) to Cmax, whereas the Cmax and tmax of clozapine were unaltered. The cotreatment increased the AUC0-t and AUC0-∞ of olanzapine by 68% and 76%, respectively, greater than those of clozapine (40% and 41%). The presence of fluvoxamine also prolonged the elimination half-life (t 1/2) of olanzapine by 40% and, to a much greater extent, clozapine by 370% but reduced the total body clearance (CL/F) of clozapine (78%) more significantly than it did for olanzapine (42%). The apparent volume of distribution (Vd) was suppressed by 31% in olanzapine combined with fluvoxamine but was unaltered in the clozapine regimen. A significant reduction in the N-desmethylclozapine to clozapine ratio was present in the clozapine with fluvoxamine regimen. The effects of fluvoxamine on different aspects of pharmacokinetics of the two antipsychotics may have implications for clinical therapeutics.en_US
dc.languageengen_US
dc.publisherSage Science Press (US). The Journal's web site is located at http://www.sagepub.com/journal.aspx?pid=169en_US
dc.relation.ispartofJournal of Clinical Pharmacologyen_US
dc.subject.meshAdulten_US
dc.subject.meshAntidepressive Agents - Adverse Effects - Blood - Pharmacokineticsen_US
dc.subject.meshAntidepressive Agents, Second-Generation - Pharmacologyen_US
dc.subject.meshArea Under Curveen_US
dc.subject.meshBenzodiazepines - Adverse Effects - Blood - Pharmacokineticsen_US
dc.subject.meshClozapine - Adverse Effects - Analogs & Derivatives - Blood - Pharmacokineticsen_US
dc.subject.meshDrug Interactionsen_US
dc.subject.meshFluvoxamine - Pharmacologyen_US
dc.subject.meshHalf-Lifeen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMetabolic Clearance Rateen_US
dc.titleThe differential effects of steady-state fluvoxamine on the pharmacokinetics of olanzapine and clozapine in healthy volunteersen_US
dc.typeArticleen_US
dc.identifier.emailZhang, ZJ: zhangzj@hkucc.hku.hken_US
dc.identifier.authorityZhang, ZJ=rp01297en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1177/0091270004266621en_US
dc.identifier.pmid15199083-
dc.identifier.scopuseid_2-s2.0-2942635933en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-2942635933&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume44en_US
dc.identifier.issue7en_US
dc.identifier.spage785en_US
dc.identifier.epage792en_US
dc.identifier.isiWOS:000222078500012-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWang, CY=35345843000en_US
dc.identifier.scopusauthoridZhang, ZJ=8061473900en_US
dc.identifier.scopusauthoridLi, WB=36066834700en_US
dc.identifier.scopusauthoridZhai, YM=7102983468en_US
dc.identifier.scopusauthoridCai, ZJ=7402902177en_US
dc.identifier.scopusauthoridWeng, YZ=7103320159en_US
dc.identifier.scopusauthoridZhu, RH=7202446723en_US
dc.identifier.scopusauthoridZhao, JP=17344801500en_US
dc.identifier.scopusauthoridZhou, HH=7404743248en_US

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