Paulzen, Michael and Haen, Ekkehard and Gruender, Gerhard and Lammertz, Sarah E. and Stegmann, Benedikt and Schruers, Koen R. J. and Walther, Sebastian and Schoretsanitis, Georgios (2016) Pharmacokinetic considerations in the treatment of hypertension in risperidone-medicated patients - thinking of clinically relevant CYP2D6 interactions. JOURNAL OF PSYCHOPHARMACOLOGY, 30 (8). pp. 803-809. ISSN 0269-8811, 1461-7285
Full text not available from this repository. (Request a copy)Abstract
Background: Treatment of arterial hypertension in patients with severe mental illnesses often results in polypharmacy, potentially leading to drug-drug interactions. The objective of the study was to analyse the in vivo inhibitory potential of two antihypertensive drugs, amlodipine and metoprolol on CYP2D6 catalysed 9-hydroxylation of risperidone (RIS). Methods: A therapeutic drug monitoring database with plasma concentrations of RIS and 9-hydroxyrisperidone (9-OH-RIS) of 1584 patients was analysed. Three groups were considered; a group of patients receiving RIS without a potentially cytochrome influencing co-medication (control group, R-0, n=852), a group co-medicated with amlodipine (R-A, n=27) and a group, co-medicated with metoprolol (R-M, n=41). Plasma concentrations, concentration-to-dose ratios (C/Ds) of RIS, 9-OH-RIS and the active moiety (AM), as well as the metabolic ratios were computed and compared using the Kruskal-Wallis test, the Mann-Whitney U test and the Jonckheere-Terpstra test to determine the means and different patterns of distribution of plasma concentrations as well as the concentration-to-dose ratios. Results: The median daily dosage of RIS did not differ between the groups (p=0.708). No differences were found in median plasma concentrations of RIS, 9-OH-RIS and AM. However, concentration-to-dose ratios for RIS, 9-OH-RIS and AM were significantly higher in the amlodipine group (p=0.025, p=0.048 and p=0.005). In the metoprolol group, the concentration-to-dose ratio for RIS was significantly higher than in the control group (p=0.017), while the C/D for 9-OH-RIS and AM was not. Conclusions and limitations: Our data show a potential pharmacokinetic interaction, most likely via CYP3A4 between amlodipine and RIS, reflected in significantly different C/Ds for RIS, 9-OH-RIS and AM. Although the interaction did not result in significantly higher plasma levels, changes in C/Ds and their distribution with regard to the median concentrations were observed.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEGATIVE SYMPTOMS; METABOLIC SYNDROME; DRUG-INTERACTIONS; SCHIZOPHRENIA; AMLODIPINE; METOPROLOL; CATIE; VARIABILITY; PREVALENCE; DISEASE; Therapeutic drug monitoring; risperidone; amlodipine; metoprolol; CYP2D6; interaction; pharmacokinetics |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Mar 2019 08:52 |
| Last Modified: | 25 Mar 2019 08:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3558 |
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