Objective: Metamizole is quite an old drug with analgesic, antipyretic and spasmolytic properties. Recent findings have shown that it may induce several cytochrome P450 enzymes, especially CYP3A4 and CYP2B6. The clinical relevance of these properties is uncertain. We aimed to unravel potential pharmacokinetic interactions between metamizole and the CYP3A4 substrate quetiapine. Methods: Plasma concentrations of quetiapine from a large therapeutic drug monitoring database were analyzed. Two groups of 33 patients, either receiving quetiapine as a monotherapy (without CYP modulating co-medications) or with concomitantly applied metamizole were compared addressing a potential impact of metamizole on the metabolism of quetiapine being reflected in differences of plasma concentrations of quetiapine and dose-adjusted plasma concentrations (C/D). Results: Patients co-medicated with metamizole showed significantly lower plasma concentrations of quetiapine (median 45.2 ng/mL, Q1=15.5; Q3=90.5 vs. 92.0 ng/mL, Q1=52.3; Q3=203.8, p=0.003). Accordingly, plasma concentrations of quetiapine in the control group were more than twice of those in the metamizole group (+103% higher). The dose-adjusted plasma concentrations were 69 % lower in the co-medication group (p=0.001). Conclusions: The combination of metamizole and quetiapine leads to significantly lower drug concentrations of quetiapine, most likely via an induction of cytochrome P450 CYP3A4 by metamizole. Clinicians have to consider the risk of adverse drug reactions, especially treatment failure under quetiapine when adding metamizole.

Objective: Combining different drugs increases the potential for drug-drug interactions en-hancing the risk of adverse drug reactions. We aimed to unravel potential pharma-cokinetic interactions between aripiprazole and duloxetine. Methods: Plasma concentrations of aripiprazole of two groups of 78 patients each, receiving aripiprazole as a monotherapy, or combined with duloxetine, were compared. A po-tential impact of duloxetine on the metabolism of aripiprazole was expected in high-er plasma concentrations of aripiprazole and higher dose-adjusted plasma concen-trations. Results: Patients co-medicated with duloxetine showed significantly higher plasma concen-trations of aripiprazole (p=0.019) by 54.2%. Dose-adjusted plasma concentrations were 45.6% higher (p=0.001). 65.4 % of these patients exhibited aripiprazole plasma concentrations above the upper limit of the therapeutic reference range, in the con-trol group this was only the case for 43.6% of the patients (p=0.006). A positive rela-tionship was found between the daily dose of duloxetine and dose-adjusted plasma concentrations of aripiprazole (p=0.034). Conclusions: Combining duloxetine and aripiprazole leads to significantly higher drug concentra-tions of aripiprazole, most likely via an inhibition of cytochrome P450 CYP2D6 and to a lesser extent of CYP3A4 by duloxetine. Clinicians have to consider increasing aripiprazole concentrations when adding duloxetine to a treatment regimen with ari-piprazole.

Objective: Metamizole is quite an old drug with analgesic, antipyretic and spasmolytic properties. Recent findings have shown that it may induce several cytochrome P450 enzymes, especially CYP3A4 and CYP2B6. The clinical relevance of these properties is uncertain. We aimed to unravel potential pharmacokinetic interactions between metamizole and the CYP3A4 substrate quetiapine. Methods: Plasma concentrations of quetiapine from a large therapeutic drug monitoring database were analyzed. Two groups of 33 patients, either receiving quetiapine as a monotherapy (without CYP modulating co-medications) or with concomitantly applied metamizole were compared addressing a potential impact of metamizole on the metabolism of quetiapine being reflected in differences of plasma concentrations of quetiapine and dose-adjusted plasma concentrations (C/D). Results: Patients co-medicated with metamizole showed significantly lower plasma concentrations of quetiapine (median 45.2 ng/mL, Q1=15.5; Q3=90.5 vs. 92.0 ng/mL, Q1=52.3; Q3=203.8, p=0.003). Accordingly, plasma concentrations of quetiapine in the control group were more than twice of those in the metamizole group (+103% higher). The dose-adjusted plasma concentrations were 69 % lower in the co-medication group (p=0.001). Conclusions: The combination of metamizole and quetiapine leads to significantly lower drug concentrations of quetiapine, most likely via an induction of cytochrome P450 CYP3A4 by metamizole. Clinicians have to consider the risk of adverse drug reactions, especially treatment failure under quetiapine when adding metamizole.

Aim: Augmentation of antipsychotic treatment with antidepressants represents a common and beneficial treatment strategy in patients suffering from schizophrenia. Combining clozapine and the selective serotonin reuptake inhibitor (SSRI) sertraline represents a clinically important strategy, but there is limited knowledge about mutual pharmacokinetic interactions. In the present study, we assessed the impact of clozapine on sertraline plasma concentrations. Methods: Based on a therapeutic drug monitoring (TDM) database, sertraline plasma concentrations were compared between two groups: patients receiving a combined treatment with sertraline and clozapine (SERTCLZ; N=15) and a matched control group receiving sertraline but no clozapine (SERT; N=17). Group differences with respect to raw and dose-adjusted plasma concentrations were assessed using non-parametric tests. Results: No significant differences were found between the groups regarding daily dosage of sertraline, age, weight, sex distribution, and caffeine or nicotine consumption (all p-values >0.05). Co-medication with clozapine was associated with 67% lower median sertraline plasma concentrations (16 vs. 48 ng/mL; p=0.022) and 28% lower median dose-adjusted plasma concentrations (C/D; 0.21 vs. 0.29 (ng/mL) / (mg/day); p=0.049) as compared to the control group. Conclusion: When applying a combined treatment with clozapine and sertraline, clinicians should consider therapeutic drug monitoring to confirm therapeutically effective plasma concentrations of sertraline.