Pharmacokinetic considerations in the treatment of hypertension in risperidone-medicated patients – thinking of clinically relevant CYP2D6 interactions. (August 2016)

• Record Type: Journal Article
• Authors: Paulzen, Michael; Haen, Ekkehard; Gründer, Gerhard; Lammertz, Sarah E; Stegmann, Benedikt; Schruers, Koen RJ; Walther, Sebastian; Schoretsanitis, Georgios
• Is Part Of: Journal of psychopharmacology. Volume 30:Number 8(2016:Aug.)
• Page Start: 803
• Page End: 809
• Publication Date: 2016-08
• Subjects: Therapeutic drug monitoring -- risperidone -- amlodipine -- metoprolol -- CYP2D6 -- interaction -- pharmacokinetics; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1177/0269881116650390
• Languages: English
• ISSNs: 0269-8811

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, 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.