Influence of Dose, Cigarette Smoking, Age, Sex, and Metabolic Activity on Plasma Clozapine Concentrations: A Predictive Model and Nomograms to Aid Clozapine Dose Adjustment and to Assess Compliance in Individual Patients

Journal of Clinical Psychopharmacology

Volumn 24, Issue 1, 2004, Pages 70-78

  Rostami Hodjegan, Amin ^a,d   Amin, Ajmal M ^b,c   Spencer, Edgar P ^b   Lennard, Martin S ^a   Tucker, Geoffrey T ^a   Flanagan, Robert J ^b  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

^b GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

^c SOUTH LONDON AND MAUDSLEY NHS FOUNDATION TRUST   (United Kingdom)

^d ROYAL HALLAMSHIRE HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CAFFEINE; CLOZAPINE; CYTOCHROME P450 1A2; CYTOCHROME P450 3A4; DRUG METABOLITE; FLUVOXAMINE; KETOCONAZOLE; NEUROLEPTIC AGENT; NORCLOZAPINE; NORTRIPTYLINE;

ADULT; AGE; AGRANULOCYTOSIS; ANALYTIC METHOD; ARTICLE; BLOOD SAMPLING; BODY WEIGHT; CALCULATION; CIGARETTE SMOKING; CONFIDENCE INTERVAL; CONTROLLED STUDY; DOSE CALCULATION; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DETERMINATION; DRUG DOSE REGIMEN; DRUG METABOLISM; EXTRAPYRAMIDAL SYMPTOM; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; MAJOR CLINICAL STUDY; MALE; MATHEMATICAL MODEL; MEASUREMENT; MULTIPLE REGRESSION; NEUTROPENIA; NOMOGRAM; PARAMETER; PATIENT COMPLIANCE; PATIENT MONITORING; PREDICTION; PRESCRIPTION; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; RETROSPECTIVE STUDY; SCHIZOPHRENIA; SEX DIFFERENCE;

ADULT; AGING; ALGORITHMS; BODY WEIGHT; CLOZAPINE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; FORECASTING; GREAT BRITAIN; HUMANS; MALE; MODELS, BIOLOGICAL; PATIENT COMPLIANCE; RETROSPECTIVE STUDIES; SEX FACTORS; SMOKING; TREATMENT OUTCOME;

EID: 1642457270     PISSN: 02710749     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.jcp.0000106221.36344.4d     Document Type: Article

References (60)

1. Marder SR. Newer antipsychotics in treatment-resistant schizophrenia. Biol Psychiatry. 1999;45:383-384.
2. Munro J, O'Sullivan D, Andrews C, et al. Active monitoring of 12,760 clozapine recipients in the UK and Ireland. Beyond pharmacovigilance. Br J Psychiatry. 1999;175:576-580.
3. Spina E, Avenoso A, Facciola G, et al. Relationship between plasma concentrations of clozapine and norclozapine and therapeutic response in patients with schizophrenia resistant to conventional neuroleptics. Psychopharmacology. 2000;148:83-89.
4. Olesen OV. Therapeutic drug monitoring of clozapine treatment. Therapeutic threshold value for serum clozapine concentrations. Clin Pharmacokinet. 1998;34:497-502.
5. Dettling M, Sachse C, Brockmoller J, et al. Long-term therapeutic drug monitoring of clozapine and metabolites in psychiatric in- and outpatients. Psychopharmacology. 2000;152:80-86.
6. Johnson TN, Rostami-Hodjegan A, Goddard JM, et al. Contribution of midazolam and its 1-hydroxy metabolite to preoperative sedation in children: a pharmacokinetic-pharmacodynamic analysis. Br J Anaesth. 2002;89:428-437.
7. Webb JA, Rostami-Hodjegan A, Abdul-Manap R, et al. Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in man: a PK-PD modelling analysis. Br J Clin Pharmacol. 2001;52:35-43.
8. Schaber G, Stevens I, Gaertner HJ, et al. Pharmacokinetics of clozapine and its metabolites in psychiatric patients: plasma protein binding and renal clearance. Br J Clin Pharmacol. 1998;46:453-459.
9. Jerling M, Merle Y, Mentre F, et al. Population pharmacokinetics of clozapine evaluated with the nonparametric maximum likelihood method. Br J Clin Pharmacol. 1997;44:447-453.
10. Eiermann B, Engel G, Johansson I, et al. The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. Br J Clin Pharmacol. 1997;44:439-446.
11. Olesen OV, Linnet K. Contributions of five human cytochrome P450 isoforms to the N-demethylation of clozapine in vitro at low and high concentrations. J Clin Pharmacol. 2001;41:823-832.
12. Özdemir V, Kalow W, Posner P, et al. CYP1A2 activity as measured by a caffeine test predicts clozapine and active metabolite steady-state concentration patients with schizophrenia. J Clin Psychopharmacol. 2001;21:398-407.
13. Bertilsson L, Carrillo JA, Dahl ML, et al. Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. Br J Clin Pharmacol. 1994;38:471-473.
14. Aitchison KJ, Gonzalez FJ, Quattrochi LC, et al. Identification of novel polymorphisms in the 5′ flanking region of CYP1A2, characterization of interethnic variability, and investigation of their functional significance. Pharmacogenetics. 2000;10:695-704.
15. Özdemir V, Kalow W, Okey AB, et al. Treatment-resistance to clozapine in association with ultrarapid CYP1A2 activity and the C-a polymorphism in intron 1 of the CYP1A2 gene: effect of grapefruit juice and low-dose fluvoxamine. J Clin Psychopharmacol. 2001;21: 603-607.
16. Sachse C, Brockmoller J, Bauer S, et al. Functional significance of a C-A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol. 1999;47:445-449.
17. Van Der Weide J, Steijns LS, Van Weelden MJ. The effect of smoking and cytochrome P450 CYP1A2 genetic polymorphism on clozapine clearance and dose requirement. Pharmacogenetics. 2003;13:169-172.
18. Gex-Fabry M, Balant-Gorgia AE, Balant LP. Therapeutic drug monitoring databases for postmarketing surveillance of drug-drug interactions. Drug Safety. 2001;24:947-959.
19. McCarthy PT, Hughes S, Paton C. Measurement of clozapine and norclozapine in plasma/serum by high performance liquid chromatography with ultraviolet detection. Biomed Chromatogr. 1995;9:36-41.
20. Armitage A, Berry G, Matthews JNS. Statistical Methods in Medical Research. Oxford: Blackwell Science, 2002.
21. Meyer JM. Individual changes in clozapine levels after smoking cessation: results and a predictive model. J Clin Psychopharmacol. 2001; 21:569-574.
22. Haring C, Meise U, Humpel C, et al. Dose-related plasma levels of clozapine: influence of smoking behaviour, sex and age. Psychopharmacology. 1989;99(suppl):S38-S40.
23. Hasegawa M, Gutierrez-Esteinou R, Way L, et al. Relationship between clinical efficacy and clozapine concentrations in plasma in schizophrenia: effect of smoking. J Clin Psychopharmacol. 1993;13:383-390.
24. Haring C, Fleischhacker WW, Schett P, et al. Influence of patient-related variables on clozapine plasma levels. Am J Psychiatry. 1990; 147:1471-1475.
25. Oyewumi LK, Cernovsky ZZ, Freeman DJ, et al. Relation of blood counts during clozapine treatment to serum concentrations of clozapine and nor-clozapine. Can J Psychiatry. 2002;47:257-261.
26. Kurz M, Hummer M, Kemmler G, et al. Long-term pharmacokinetics of clozapine. Br J Psychiatry. 1998;173:341-344.
27. Perry PJ, Bever KA, Arndt S, et al. Relationship between patient variables and plasma clozapine concentrations: a dosing nomogram. Biol Psychiatry. 1998;44:733-738.
28. Wetzel H, Anghelescu I, Szegedi A, et al. Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: differential effects of fluvoxamine and paroxetine in a prospective study. J Clin Psychopharmacol. 1998;18:2-9.
29. Palego L, Biondi L, Giannaccini G, et al. Clozapine, norclozapine plasma levels, their sum and ratio in 50 psychotic patients: influence of patient-related variables. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:473-480.
30. Lane HY, Jann MW, Chang YC, et al. Repeated ingestion of grapefruit juice does not alter clozapine's steady-state plasma levels, effectiveness, and tolerability. J Clin Psychiatry. 2001;62:812-817.
31. Kuss H. TDM of clozapine: influence of co-medication, Proceedings of VII World Conference on Clinical Pharmacology and Therapeutics, Florence 15-20 July, Italy, 2000. Blackwell Science, Oxford. p. 108.
32. Zullino DF, Delessert D, Eap CB, et al. Tobacco and cannabis smoking cessation can lead to intoxication with clozapine or olanzapine. Int Clin Psychopharmacol. 2002;17:141-143.
33. Seppala NH, Leinonen EVJ, Lehtonen ML, et al. Clozapine serum concentrations are lower in smoking than in nonsmoking schizophrenic patients. Pharmacol Toxicol. 1999;85:244-246.
34. Gaertner I, Gaertner HJ, Vonthein R, et al. Therapeutic drug monitoring of clozapine in relapse prevention: a five-year prospective study. J Clin Psychopharmacol. 2001;21:305-310.
35. Hagg S, Spigset O, Mjorndal T, et al. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2000;49: 59-63.
36. Carrillo JA, Herraiz AG, Ramos SI, et al. Effects of caffeine withdrawal from the diet on the metabolism of clozapine in schizophrenic patients. J Clin Psychopharmacol. 1998;18:311-316.
37. Lammers CH, Deuschle M, Weigmann H, et al. Co-administration of clozapine and fluvoxamine in psychotic patients-clinical experience. Pharmacopsychiatry. 1999;32:76-77.
38. Jerling M, Lindstrom L, Bondesson U, et al. Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. Ther Drug Monit. 1994; 16:368-374.
39. Chang WH, Augustin B, Lane HY, et al. In-vitro and in-vivo evaluation of the drug-drug interaction between fluvoxamine and clozapine. Psychopharmacology. 1999;145:91-98.
40. Lane HY, Chiu CC, Kazmi Y, et al. Lack of CYP3A4 inhibition by grapefruit juice and ketoconazole upon clozapine administration in vivo. Drug Metab Drug Interac. 2001;18:263-278.
41. Facciola G, Avenoso A, Scordo MG, et al. Small effects of valproic acid on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenic or affective disorders. Ther Drug Monit. 1999;21:341-345.
42. Miller DD, Fleming F, Holman TL, et al. Plasma clozapine concentrations as a predictor of clinical response: a follow-up study. J Clin Psychiatry. 1994;55(suppl B):117-121.
43. Raaska K, Neuvonen PJ. Ciprofloxacin increases serum clozapine and N-desmethylclozapine: a study in patients with schizophrenia. Eur J Clin Pharmacol. 2000;56:585-589.
44. Raaska K, Neuvonen PJ. Serum concentrations of clozapine and N-desmethylclozapine are unaffected by the potent CYP3A4 inhibitor itraconazole. Eur J Clin Pharmacol. 1998;54:167-170.
45. Guitton C, Abbar M, Kinowski JM, et al. Multiple-dose pharmacokinetics of clozapine in patients with chronic schizophrenia. J Clin Psychopharmacol. 1998;18:470-476.
46. Spina E, Avenoso A, Salemi M, et al. Plasma concentrations of clozapine and its major metabolites during combined treatment with paroxetine or sertraline. Pharmacopsychiatry. 2000;33:213-217.
47. Hinze-Selch D, Deuschle M, Weber B, et al. Effect of coadministration of clozapine and fluvoxamine versus clozapine monotherapy on blood cell counts, plasma levels of cytokines and body weight. Psychopharmacology. 2000;149:163-169.
48. Lovdahl MJ, Perry PJ, Miller DD. The assay of clozapine and N-desmethylclozapine in human plasma by high-performance liquid chromatography. Ther Drug Monit. 1991;13:69-72.
49. Lin G, McKay G, Hubbard JW, et al. Decomposition of clozapine N-oxide in the qualitative and quantitative analysis of clozapine and its metabolites. J Pharmacol Sci. 1994;83:1412-1417.
50. Rostami-Hodjegan A, Foster DJR, Charlier C, et al. A meta-analysis of the dose-concentration relationship for methadone and a nomogram to assess compliance and metabolic variability. J Psychopharmacol. 2001; 15(suppl):A35.
51. de Leon J, Dadvand M, Canuso C, et al. Schizophrenia and smoking: an epidemiological survey in a state hospital. Am J Psychiatry. 1995; 152:453-455.
52. McCarthy RH. Seizures following smoking cessation in a clozapine responder. Pharmacopsychiatry. 1994;27:210-211.
53. Ziedonis DM, Kosten TR, Glazer WM, et al. Nicotine dependence and schizophrenia. Hosp Community Psychiatry. 1994;45:204-206.
54. Goff DC, Henderson DC, Amico E. Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. Am J Psychiatry. 1992;149:1189-1194.
55. Carrillo JA, Christensen M, Ramos SI, et al. Evaluation of caffeine as an in vivo probe for CYP1A2 using measurements in plasma, saliva, and urine. Ther Drug Monit. 2000;22:409-417.
56. Relling MV, Lin JS, Ayers GD, et al. Racial and gender differences in N-acetyltransferase, xanthine oxidase, and CYP1A2 activities. Clin Pharmacol Ther. 1992;52:643-658.
57. Tantcheva-Poor I, Zaigler M, Rietbrock S, et al. Estimation of cytochrome P-450 CYP1A2 activity in 863 healthy Caucasians using a saliva-based caffeine test. Pharmacogenetics. 1999;9:131-144.
58. Welfare MR, Aitkin M, Bassendine MF, et al. Detailed modelling of caffeine metabolism and examination of the CYP1A2 gene: lack of a polymorphism in CYP1A2 in Caucasians. Pharmacogenetics. 1999; 9:367-375.
59. Chung WG, Kang JH, Park CS, et al. Effect of age and smoking on in vivo CYP1A2, flavin-containing monooxygenase, and xanthine oxidase activities in Koreans: determination by caffeine metabolism. Clin Pharmacol Ther. 2000;67:258-266.
60. Piscitelli SC, Frazier JA, McKenna K, et al. Plasma clozapine and haloperidol concentrations in adolescents with childhood-onset schizophrenia: association with response. J Clin Psychiatry. 1994;55(suppl B): 94-97.