Pharmacokinetic considerations in the treatment of hypertension in risperidone-medicated patients - thinking of clinically relevant CYP2D6 interactions

Paulzen, Michael; Haen, Ekkehard; Gründer, Gerhard; Lammertz, Sarah E; Stegmann, Benedikt; Schruers, Koen Rj; Walther, Sebastian; 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. Sage Publications 10.1177/0269881116650390

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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, R0, n=852), a group co-medicated with amlodipine (RA, n=27) and a group, co-medicated with metoprolol (RM, 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:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Translational Research Center
04 Faculty of Medicine > University Psychiatric Services

UniBE Contributor:

Walther, Sebastian and Schoretsanitis, Georgios

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0269-8811

Publisher:

Sage Publications

Language:

English

Submitter:

Sebastian Walther

Date Deposited:

09 Aug 2016 15:41

Last Modified:

16 Dec 2016 09:00

Publisher DOI:

10.1177/0269881116650390

PubMed ID:

27251417

Uncontrolled Keywords:

CYP2D6; Therapeutic drug monitoring; amlodipine; interaction; metoprolol; pharmacokinetics; risperidone

URI:

https://boris.unibe.ch/id/eprint/85587

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