Investigation of metabolite to parent compound ratios of venlafaxine and risperidone in minors

Introduction The Serotonin and Norepinephrine Reuptake Inhibitor (SNRI) venlafaxine (VEN) and the atypical antipsychotic risperidone (RIS) are widely used in the treatment of psychiatric patients. VEN and RIS serum concentrations and the respective active metabolite (desmethylvenlafaxin (DVEN) and 9-hydroxyrisperidone (9OHRIS)) as well as their metabolite to parent compound ratio (MPR) reflect CYP2D6 activity. In the literature, age-related differences in CYP2D6 activity are discussed. Until now, no MPRs of VEN and RIS in minors have been described yet. The aim of the present study was to analyze and describe the MPR of VEN and RIS in order to investigate the impact of age on the serum concentration of VEN and RIS and their active metabolites.

Methods Serum level determinations of VEN and RIS were performed at the Center of Mental Health of the University Hospital of Wuerzburg, Germany, of the Departments Child and Adolescents Psychiatry and Psychiatry, Psychosomatics and Psychotherapy during the years 2015 – 2019 were retrospectively assessed. Serum concentrations of patients with CYP2D6 influencing comedication and patients demonstrating non-adherence such as no detectable serum concentrations were excluded from analysis.

Results First preliminary results in minors (n = 27) showed mean VEN daily dose of 140 mg/d ± 73 mg/d with a mean VEN serum concentration of 58.8 ng/ml ± 60.3 ng/ml and DVEN serum concentration of 125.3 ng/ml ± 61.5 ng/ml. Mean RIS daily dose (n = 79) was 2.0 mg/d ± 1.3 mg/d with a mean RIS serum concentration of 3.3 ng/ml ± 5.8 ng/ml and mean 9OHRIS serum concentration of 12.9 ng/ml ± 12.3 ng/ml. MPR in minors of VEN (age 12 – 17 years) was 4.69 (SD 5.02, range 0.28 – 25.0), MPR of RIS (age 8 – 17 years) was 8.82 (SD 12.35, range 0 – 69).

Conclusion The results of MPR might be helpful for laboratory interpretation of serum concentrations during treatment with VEN or RIS in minors by identifying CYP2D6 abnormalities or pharmacokinetic interactions. The determination of serum concentrations and the knowledge of MPR might predict and avoid adverse drug reactions in children and adolescents.

 

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