Discovering interactions in augmentation strategies: Impact of duloxetine on the metabolism of aripiprazole

被引:3
作者
Margraff, Teresa [1 ,2 ]
Schoretsanitis, Georgios [3 ,4 ,5 ]
Neuner, Irene [1 ,2 ]
Haen, Ekkehard [6 ,7 ,8 ]
Gaebler, Arnim Johannes [1 ,2 ,9 ]
Paulzen, Michael [1 ,2 ,10 ]
机构
[1] Univ Hosp RWTH Aachen, Dept Psychiat Psychotherapy & Psychosomat, Aachen, Germany
[2] Rhein Westfal TH Aachen, JARA Translat Brain Med, Aachen, Germany
[3] Univ Zurich, Psychiat Univ Hosp Zurich, Dept Psychiat Psychotherapy & Psychosomat, Zurich, Switzerland
[4] Northwell Hlth, Zucker Hillside Hosp, Dept Psychiat, Glen Oaks, NY USA
[5] Zucker Sch Med Hofstra Northwell, Dept Psychiat & Mol Med, Hempstead, NY USA
[6] Univ Regensburg, Dept Psychiat & Psychotherapy, Clin Pharmacol, Regensburg, Germany
[7] Univ Regensburg, Dept Pharmacol & Toxicol, Regensburg, Germany
[8] AGATE gGmbH, Clin Pharmacol Inst, Pentling, Germany
[9] Univ Hosp RWTH Aachen, Inst Physiol, Aachen, Germany
[10] Alexianer Hosp Aachen, Alexianergraben 33, D-52062 Aachen, Germany
关键词
aripiprazole; cytochrome; duloxetine; interaction; pharmacokinetics; therapeutic drug monitoring; DRUG-DRUG INTERACTIONS; SERUM CONCENTRATIONS; ADJUNCTIVE TREATMENT; PARTIAL AGONIST; ADD-ON; RISPERIDONE; SCHIZOPHRENIA; PHARMACOKINETICS; COMEDICATION; EFFICACY;
D O I
10.1111/bcpt.13875
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
ObjectiveWe aimed to unravel potential pharmacokinetic interactions between aripiprazole and duloxetine. MethodsPlasma concentrations of aripiprazole in two groups of 78 patients each, receiving aripiprazole as a monotherapy or combined with duloxetine, were compared. A potential impact of duloxetine on the metabolism of aripiprazole was expected in higher plasma concentrations of aripiprazole and higher dose-adjusted plasma concentrations. ResultsPatients co-medicated with duloxetine showed significantly higher plasma concentrations of aripiprazole by 54.2% (p = 0.019). Dose-adjusted plasma concentrations were 45.6% higher (p = 0.001); 12.8% of these patients exhibited aripiprazole plasma concentrations above the upper limit of the therapeutic reference range, in the control group this was only the case for 10.3% of the patients. A positive relationship was found between the daily dose of duloxetine and dose-adjusted plasma concentrations of aripiprazole (p = 0.034). As dehydroaripiprazole concentrations were not available, conclusions for the active moiety (aripiprazole plus dehydroaripiprazole) could not be drawn. ConclusionsCombining duloxetine and aripiprazole leads to significantly higher drug concentrations of aripiprazole, most likely via an inhibition of cytochrome P450 CYP2D6 and to a lesser extent of CYP3A4 by duloxetine. Clinicians have to consider increasing aripiprazole concentrations when adding duloxetine to a treatment regimen with aripiprazole.
引用
收藏
页码:73 / 81
页数:9
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