Body mass index (BMI) but not body weight is associated with changes in the metabolism of risperidone; A pharmacokinetics-based hypothesis

Paulzen, Michael; Haen, Ekkehard; Stegmann, Benedikt; Hiemke, Christoph; Gründer, Gerhard; Lammertz, Sarah E.; Schoretsanitis, Georgios

doi:10.1016/j.psyneuen.2016.07.009

Cited by 32 publications

(25 citation statements)

References 34 publications

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“…In the above groupings, it is interesting to underline that dosing differed significantly, while it did not in the male vs. female comparison. This notion contrasts previous findings of RIS adult pharmacokinetics, where BMI and not weight displayed crucial effects [32]. Thus, our knowledge of adults RIS pharmacokinetics cannot be automatically transferred to children and adolescents.…”

Section: Discussioncontrasting

confidence: 72%

“…Thus, our knowledge of adults RIS pharmacokinetics cannot be automatically transferred to children and adolescents. It seems that, unlike adults, BMI does not precisely reflect pharmacokinetically-relevant parameters such as drug distribution volume in children [32]. On the other hand, weight seems to be crucial; low-weight patients had lower ratios and higher C/D 9-OH-RIS concentrations than patients with higher weight.…”

Section: Discussionmentioning

confidence: 94%

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Plasma Risperidone-related Measures in Children and Adolescents with Oppositional Defiant/Conduct Disorders

Piacentino

Kotzalidis

Schoretsanitis

et al. 2020

Clin Psychopharmacol Neurosci

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Objective: Therapeutic drug monitoring helps clinicians in choosing the right drug and adjust its dose in specific patients. To this end, we aimed to assess time patterns of risperidone and its metabolite, 9-hydroxyrisperidone, in children and adolescents with oppositional defiant and/or conduct disorder. Methods: We measured plasma concentrations of risperidone and 9-hydroxyrisperidone, their sum (active moiety, AM) and ratio, as well as plasma concentrations corrected for daily dose (C/D), from 140 children/adolescents with the above-mentioned disorders. We used Student's t test to compare females versus males, patients under versus over 16-year-old, patients with lower versus higher than the median body weight, and patients with lower versus higher than the median body mass index (BMI). Two mixed-effects logistic regression models were fitted for risperidone/9hydroxyrisperidone ratio and AM, respectively, by considering risperidone daily dose and patients' demographic characteristics. Results: Females had higher 9-hydroxyrisperidone and AM plasma concentrations than males (p = 0.004 and p = 0.034). Younger patients had lower risperidone plasma concentration and risperidone/9-hydroxyrisperidone ratio (p = 0.02 and p = 0.021), but higher C/D 9-hydroxyrisperidone and AM than older patients (p = 0.013 and p = 0.043). Lower-weight patients had lower plasma risperidone and risperidone/9-hydroxyrisperidone ratio (p = 0.014 and p = 0.019), but higher C/D 9-hydroxyrisperidone concentration than heavier patients (p = 0.03). All these results could be accounted for by daily dose. Patients with lower and higher BMI did not differ significantly. Regression analyses showed that only risperidone daily dose predicted risperidone/9-hydroxyrisperidone ratio, whereas risperidone daily dose, sex, and age predicted AM. Conclusion: Clinicians prescribing risperidone need to consider sex, age, and weight, but not BMI when adjusting daily doses.

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Section: Discussioncontrasting

confidence: 72%

Section: Discussionmentioning

confidence: 94%

Plasma Risperidone-related Measures in Children and Adolescents with Oppositional Defiant/Conduct Disorders

Piacentino

Kotzalidis

Schoretsanitis

et al. 2020

Clin Psychopharmacol Neurosci

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“…Therapeutic drug monitoring databases are a valuable source for promoting the safety and tolerability of pharmacotherapy in a clinical setting. Furthermore, the evaluation of databases of drug concentrations allows many interesting pharmacokinetic and/or clinical issues to be addressed, such as DDIs , the effect of smoking on drug concentrations , adverse drug reactions and clinical topics such as treatment responses in correlation with pharmacokinetic patterns of drug concentrations in patients' blood . As data on the pharmacokinetics of perazine (e.g.…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450‐mediated interaction between perazine and risperidone: implications for antipsychotic polypharmacy

Paulzen

Haen

Hiemke

et al. 2017

Brit J Clinical Pharma

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“…For a better understanding of potentially occurring DDIs in complex multiple drug therapy settings, data from TDM surveys are an ideal source for identification and quantification of risks. 55,56 In our naturalistic sample, patients on a stable dose with RIS in the control group and patients that were comedicated with VPA, C/D values for RIS in the R LMT group were significantly higher than in the control group (uncorrected P = 0.021 for Mann-Whitney U test). ‡ C/D values for 9-OH-RIS and RIS + 9-OH-RIS in the R CBZ group were significantly lower than in the control group (uncorrected P < 0.001 and P < 0.001 for Mann-Whitney U test).…”

Section: Discussionmentioning

confidence: 86%

“…For a better understanding of potentially occurring DDIs in complex multiple drug therapy settings, data from TDM surveys are an ideal source for identification and quantification of risks. 55,56 In our naturalistic sample, patients on a stable dose with RIS in the control group and patients that were comedicated with VPA, FIGURE 1. Median plasma concentrations of RIS, 9-OH-RIS and active moiety as well as the metabolic ratios (RIS/9-OH-RIS) in the 4 different study groups.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Drug-Drug Interactions of Mood Stabilizers and Risperidone in Patients Under Combined Treatment

Schoretsanitis¹,

Haen²,

Gründer³

et al. 2016

J Clin Psychopharmacol

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Background: The combination of anticonvulsant mood stabilizers with antipsychotic drugs may lead to clinically relevant drug-drug interactions. The objective of the study was to identify pharmacokinetic interactions of different mood stabilizers on the metabolism of risperidone (RIS) under natural conditions.Methods: A large therapeutic drug monitoring database containing plasma concentrations of RIS and its metabolite 9-hydroxy-RIS (9-OH-RIS) of 1,584 adult patients was analyzed. Four groups (n = 1,072) were compared: a control group without a potentially cytochrome interacting comedication (R 0 , n = 852), a group comedicated with valproate (VPA) (R VPA , n = 153), a group comedicated with lamotrigine (LMT) (R LMT , n = 46), and a group under concomitant medication with carbamazepine (CBZ) (R CBZ , n = 21). Dose-adjusted plasma concentrations (C/D ratio) for RIS, 9-OH-RIS and active moiety (AM) (RIS + 9-OH-RIS), as well as metabolic ratios (RIS/9-OH-RIS) were computed.Results: Groups did not differ with regard to the daily dosage (P = 0.46).Differences were detected for the distributions of the C/D ratios for RIS, 9-OH-RIS and AM (P = 0.003, P < 0.001 and P < 0.001, respectively). Differences remained significant after conducting a Bonferroni correction (P = 0.0125). Pairwise comparisons of the concomitant medication groups with the control group revealed significant differences; RIS C/D ratios were significantly higher in the VPA and the LMT group than in the control group (P = 0.013; P = 0.021). However, these differences did not remain significant after Bonferroni correction. In contrast, CBZ-treated patients showed lower dose-adjusted plasma concentrations of 9-OH-RIS (P < 0.001) as well as the AM (P < 0.001) than the control group; this difference survived the Bonferroni correction. Conclusions:The data give evidence for pharmacokinetic interactions between RIS and different anticonvulsant mood stabilizers. Carbamazepine decreased serum concentrations of 9-OH-RIS and the AM when compared with the control group. In case of VPA and LMT, findings were less significant; hints for a weak RIS metabolism inhibition by LMT of unclear clinical significance were found.Key Words: therapeutic drug monitoring, risperidone, carbamazepine, valproic acid, lamotrigine cytochrome P450, interaction, pharmacokinetics (J Clin Psychopharmacol 2016;36: 00-00) G uidelines worldwide recommend the coadministration of second-generation antipsychotics as augmentative therapy to mood stabilizers or vice versa in the treatment of bipolar disorders, especially for the treatment of manic episodes.1-3 Acceptance of this strategy which promises better efficacy 4 despite a higher potential of adverse events 5,6 is reflected in increasing prescription trends. 7 Many pharmacokinetic drug-drug interactions (DDIs) have been identified by therapeutic drug monitoring (TDM) as TDM databases enable evaluation of pharmacokinetic DDIs in a representative population to get an insight into the safety and tolerability of combined psychopharmacological ...

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Body mass index (BMI) but not body weight is associated with changes in the metabolism of risperidone; A pharmacokinetics-based hypothesis

Cited by 32 publications

References 34 publications

Plasma Risperidone-related Measures in Children and Adolescents with Oppositional Defiant/Conduct Disorders

Plasma Risperidone-related Measures in Children and Adolescents with Oppositional Defiant/Conduct Disorders

Cytochrome P450‐mediated interaction between perazine and risperidone: implications for antipsychotic polypharmacy

Pharmacokinetic Drug-Drug Interactions of Mood Stabilizers and Risperidone in Patients Under Combined Treatment

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