Schoretsanitis, Georgios and Haen, Ekkehard and Gruender, Gerhard and Stegmann, Benedikt and Schruers, Koen R. J. and Hiemke, Christoph and Lammertz, Sarah E. and Paulzen, Michael (2016) Pharmacokinetic Drug-Drug Interactions of Mood Stabilizers and Risperidone in Patients Under Combined Treatment. JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY, 36 (6). pp. 554-561. ISSN 0271-0749, 1533-712X
Full text not available from this repository. (Request a copy)Abstract
Background: The combination of anticonvulsant mood stabilizers with antipsychotic drugs may lead to clinically relevant drug-drug interactions. The objective of the study was to identify pharmacokinetic interactions of different mood stabilizers on the metabolism of risperidone (RIS) under natural conditions. Methods: A large therapeutic drug monitoring database containing plasma concentrations of RIS and its metabolite 9-hydroxy-RIS (9-OH-RIS) of 1,584 adult patients was analyzed. Four groups (n = 1,072) were compared: a control group without a potentially cytochrome interacting comedication (R-0, n = 852), a group comedicated with valproate (VPA) (RVPA, n = 153), a group comedicated with lamotrigine (LMT) (R-LMT, n = 46), and a group under concomitant medication with carbamazepine (CBZ) (R-CBZ, n = 21). Dose-adjusted plasma concentrations (C/D ratio) for RIS, 9-OH-RIS and active moiety (AM) (RIS + 9-OH-RIS), as well as metabolic ratios (RIS/9-OH-RIS) were computed. Results: Groups did not differ with regard to the daily dosage (P = 0.46). Differences were detected for the distributions of the C/D ratios for RIS, 9-OH-RIS and AM(P = 0.003, P < 0.001 and P < 0.001, respectively). Differences remained significant after conducting a Bonferroni correction (P = 0.0125). Pairwise comparisons of the concomitant medication groups with the control group revealed significant differences; RIS C/D ratios were significantly higher in the VPA and the LMT group than in the control group (P = 0.013; P = 0.021). However, these differences did not remain significant after Bonferroni correction. In contrast, CBZ-treated patients showed lower dose-adjusted plasma concentrations of 9-OH-RIS (P < 0.001) as well as the AM (P < 0.001) than the control group; this difference survived the Bonferroni correction. Conclusions: The data give evidence for pharmacokinetic interactions between RIS and different anticonvulsant mood stabilizers. Carbamazepine decreased serum concentrations of 9-OH-RIS and the AM when compared with the control group. In case of VPA and LMT, findings were less significant; hints for a weak RIS metabolism inhibition by LMT of unclear clinical significance were found.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CYTOCHROMES P450 2D6; LONG-TERM TREATMENT; BIPOLAR DISORDER; PLASMA-CONCENTRATIONS; VALPROIC ACID; 2ND-GENERATION ANTIPSYCHOTICS; CONCOMITANT CARBAMAZEPINE; PSYCHIATRIC-DISORDERS; BODY-WEIGHT; CYP2D6; therapeutic drug monitoring; risperidone; carbamazepine; valproic acid; lamotrigine cytochrome P450; interaction; pharmacokinetics |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Apr 2019 13:39 |
| Last Modified: | 10 Apr 2019 13:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3910 |
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