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Clinical Drug Investigation
Published in: Clinical Drug Investigation 4/2000

01-04-2000 | Clinical Pharmacodynamics

Risperidone Drug Monitoring

A Useful Clinical Tool?

Authors: Dr Pascal Odou, J. C. Levron, M. Luyckx, C. Brunet, Hugues Robert

Published in: Clinical Drug Investigation | Issue 4/2000

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Abstract

Background: Risperidone is an atypical antipsychotic drug that has been marketed in France since 1996. Therapeutic failures have been observed with risperidone.
Objective: To investigate whether interactions with the cytochrome P450 (CYP) isoenzymes implicated in risperidone metabolism could explain these treatment failures.
Design and Setting: This was a retrospective study of clinical and drug monitoring data from 50 patients treated by five psychiatrists in northern France.
Methods: The concentration of active drug (risperidone + 9-hydroxy-risperidone) in serum was evaluated by high performance liquid chromatography and radio receptor assay. Clinical efficacy was assessed by the global improvement (CGI2) item of the Clinical Global Impression rating scale.
Results: Statistical analysis revealed a significant increase in efficacy when the serum concentration of active drug was between 25 and 150 μg/L compared with when it was out of this range. Carbamazepine, a CYP3A4 inducer, dramatically decreased the concentration of the active moiety of risperidone; on the contrary, CYP3A4 inhibitors (alprazolam and valproic acid) increased the concentration of active drug. The metabolism of risperidone by CYP3A4 did not lead to the formation of metabolite(s) with anti-D2 dopaminergic activity. Drugs interacting with CYP2D6 altered the risperidone/9-hydroxy-risperidone ratio but did not change the total amount of active drug.
Conclusions: We have established a therapeutic range for risperidone. CYP3A4 is a major pathway for risperidone metabolism. Consideration of these factors in clinical practice should lead to improved outcomes for patients treated with risperidone.
Literature
1.
Leysen JE, Janssen PMF, Schotte A, et al. Interaction of anti-psychotic drugs with neurotransmitter receptor sites in vitro and in vivo in relation to pharmacological and clinical effects: role of 5HT2 receptors. Psychopharmacology 1993; 112: S40–S54PubMedCrossRef
2.
Ereshefsky L, Lacombe S. Pharmacological profile of risperidone. Can J Psychiatry 1993; 38Suppl. 3: S80–8PubMed
3.
Borison RL. Risperidone: pharmacokinetics. J Clin Psychiatry Monogr 1994; 14(3): 253–5
4.
Heykants J, Huang M-L, Mannens G, et al. The pharmacokinetics of risperidone in humans: a summary. Clin Psychiatry 1994; 55Suppl. 5: 13–7
5.
Mannens G, Huang ML, Meudermans W, et al. Absorption, metabolism and excretion of risperidone in humans. Drug Metab Dispos 1993; 21(6): 1134–40PubMed
6.
Ereshefsky L. Pharmacokinetics and drug interactions: update for new antipsychotics. J Clin Psychiatry 1996; 57Suppl. 11: 12–25PubMed
7.
Van Peer A, Meuldermans W, Woestenborghs R, et al. Clinical pharmacokinetics of risperidone. In: Kane JM, Möller HJ, Awouters F, editors. Serotonin in antipsychotic treatment: mechanisms and clinical practice. New York; Marcel Dekker, 1996: 277–91
8.
Barges-Bertocchio MH, Pupeschi G, Levron JC, et al. Carbama-zepine (CBZ) induces the metabolism of risperidone, a novel antipsychotic. Proceedings of the Fifth European ISSX Meeting; 1993 Sep 26–29: Vol. 3, no. 186: 186
9.
Lane HY, Chang WH. Risperidone-carbamazepine interactions: is cytochrome P450 3A involved? J Clin Psychiatry 1998; 59(8): 430–1PubMedCrossRef
10.
11.
Chong SA, Tan CH, Lee EL, et al. Augmentation of risperidone with valproic acid. J Clin Psychiatry 1998; 59(8): 430–1PubMedCrossRef
12.
Guy W. ECDEU Assessment Manual for Psychopharmacology: Publication ADM 76-338, Rockville, (MD): US Department of Health, Education and Welfare, 1976: 217–22
13.
Woestenborghs R, Lorreyne W, Van Rompaey F, et al. Determination of risperidone and 9-hydroxyrisperidone in plasma, urine and animal tissues by high-performance liquid chromatography. J Chromatogr 1992 December; 583(2): 223–30PubMedCrossRef
14.
Odou P, Vaiva G, Luyckx M, et al. Neuroleptics monitoring relation between antipsychotic efficiency and radioreceptor assay concentrations. Eur J Clin Pharmacol 1996; 50: 357–63PubMedCrossRef
15.
Bertchy G, Vandel S, Jounet JM, et al. Interaction valpromide-amytriptilline: augmentation de l’amitrytilline et de la nortriptylline par le valpromide. Encéphale 1990; 16: 43–5
16.
Nemeroff CB, De Vane CL, Pollock BG. Newer antidepressants and the cytochrome P450 system. Am J Psychiatry 1996 March; 153(3): 311–20PubMed
17.
Ring BJ, Binkley SN, Vandenbranden M, et al. In vitro interaction of the antipsychotic agent olanzapine with human cytochromes P450 CYP2C9, CYP2C19, CYP2D6 and CYP3A. Br J Clin Pharmacol 1996 March; 41(3): 181–6PubMedCrossRef
18.
Yeates RA, Scharpf F, Laufen H, et al. Screening for cytochrome P450 3 A in man: studies with midazolam and nefidipine. J Pharm Pharmacol 1996 Sept; 48(9): 933–4PubMedCrossRef
19.
Koley AP, Robinson RC, Markowitz A, et al. Drug-drug interactions: effect of quinidine on nifedipine binding to human cytochrome P450 3A4. Biochem Pharmacol 1997 Feb 21; 53(4): 455–60PubMedCrossRef
20.
Fischer V, Vogels B, Maurer G, et al. The antipsychotic clozapine is metabolized by the polymorphic human microsomal and recombinant cytochrome P450 2D6. J Pharmacol Exp Ther 1992 Mar; 260(3): 1355–60PubMed
21.
Linnet K., Olesen OV. Metabolism of clozapine by cDNA-expressed human cytochrome P450 enzymes. Drug Metab Dispos 1997 Dec; 25(12): 1379–82PubMed
22.
Aravagiri M, Marder SR, Wirshing D, et al. Plasma concentrations of risperidone and its 9 hydroxy metabolite and their relationship to dose in schizophrenic patients: simultaneous determination by a high performance liquid chromatography with electrochemical detection. Pharmacopsychiatry 1998; 31: 102–9PubMedCrossRef
23.
Darby JK, Pasta DJ, Elfand L, et al. Risperidone dose and blood level variability: accumulation effects and interindividual and intraindividual variability in the non responder patient in the clinical practice setting. J Clin Psychopharmacol 1997; 17(6): 478–84PubMedCrossRef
24.
Bondolfi G, Baumann P, Dufours H. Treatment resistant schizophreny: clinical experience with new antipsychotics. Eur Neuropharmacol 1996; 6(2): 521–5
25.
Perry PJ, Miller DD, Arndt SV, et al. Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients. Am J Psychiatry 1991; 148: 231–5PubMed
26.
Pikar D, Owen RR, Litman RE, et al. Clinical and biologic response to clozapine in patients with schizophrenia. Arch Gen Psychiatry 1992; 49: 345–53CrossRef
27.
Odou P, Frimat B, Fontaine B, et al. Determination of clozapine in serum by receptor assay versus high performance liquid chromatography: possible detection of hydroxy-metabolites. J Clin Pharm Ther 1996; 21: 337–42PubMedCrossRef
28.
Davis JM, Ericksen SE, Hurt S, et al. Haloperidol plasma levels and clinical response: basic concepts and clinical data. Psychopharmacol Bull 1985; 21: 48–51PubMed
29.
Mavroïdis ML, Kanter DR, Hirschowitz J. Plasma haloperidol levels and clinical response: confounding variables. Psychopharmacol Bull 1985; 21: 61–5
30.
Smith RC, Vroulis G, Shvartsburg A, et al. RBC and plasma haloperidol and clinical response in schizophrenia. Am J Psychiatry 1982; 139: 1054–6PubMed
31.
Van Putten T, Marder SR, Mintz J, et al. Haloperidol plasma levels and clinical response: a therapeutic window relationship. Am J Psychiatry 1992: 500-5
32.
Miller DD, Hershey LA, Duffy JP. Serum haloperidol concentrations and clinical response in acute psychosis. Drug Intell Clin Pharm 1983; 17: 445
33.
Dalh SG. Plasma level monitoring of antipsychotic drugs. Clinical utility. Clin Pharmacokinet 1986; 11: 36–61CrossRef
34.
Balant-Giorgia AE, Gex-Fabry M, Genet C, et al. Therapeutic drug monitoring of risperidone using a new, rapid HPLC method: reappraisal of interindividual variability factors. Ther Drug Monit 1999; 21: 105–15CrossRef
35.
Fang J, Bourin M, Baker GB. Metabolism of risperidone to 9 hydroxyrisperidone by human cytochromes P450 2D6 and 3A4. Naunyn Schmiedebergs Arch Pharmacol 1999 Feb; 359(2): 147–51PubMedCrossRef
Metadata
Title
Risperidone Drug Monitoring
A Useful Clinical Tool?
Authors
Dr Pascal Odou
J. C. Levron
M. Luyckx
C. Brunet
Hugues Robert
Publication date
01-04-2000
Publisher
Springer International Publishing
Published in
Clinical Drug Investigation / Issue 4/2000
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI
https://doi.org/10.2165/00044011-200019040-00006

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