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Titolo:
Effects of gender and age on plasma levels of clozapine and its metabolites: Analyzed by critical statistics
Autore:
Lane, HY; Chang, YC; Chang, WH; Lin, SK; Tseng, YT; Jann, MW;
Indirizzi:
Taipei City Psychiat Ctr, Lab Biol Psychiat, Taipei 110, Taiwan Taipei City Psychiat Ctr Taipei Taiwan 110 Psychiat, Taipei 110, Taiwan Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan Natl Def Med Ctr Taipei Taiwan Ctr, Grad Inst Life Sci, Taipei, Taiwan Tamkang Univ, Dept Math, Taipei, Taiwan Tamkang Univ Taipei TaiwanTamkang Univ, Dept Math, Taipei, Taiwan Mercer Univ, Sch Pharm, So Sch Pharm, Atlanta, GA USA Mercer Univ AtlantaGA USA niv, Sch Pharm, So Sch Pharm, Atlanta, GA USA
Titolo Testata:
JOURNAL OF CLINICAL PSYCHIATRY
fascicolo: 1, volume: 60, anno: 1999,
pagine: 36 -
SICI:
0160-6689(199901)60:1<36:EOGAAO>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
REFRACTORY SCHIZOPHRENIC-PATIENTS; PERFORMANCE LIQUID-CHROMATOGRAPHY; N-DESMETHYLCLOZAPINE; CLINICAL-RESPONSE; ULTRAVIOLET DETECTION; PHARMACOKINETICS; EFFICACY; SMOKING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Social & Behavioral Sciences
Clinical Medicine
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Chang, WH Taipeiiwany Psychiat Ctr, Lab Biol Psychiat, 309 Sung Te Rd, Taipei 110, Ta Taipei City Psychiat Ctr 309 Sung Te Rd Taipei Taiwan 110 0, Ta
Citazione:
H.Y. Lane et al., "Effects of gender and age on plasma levels of clozapine and its metabolites: Analyzed by critical statistics", J CLIN PSY, 60(1), 1999, pp. 36

Abstract

Background: Previous reports concerning the effects of gender and age on steady-state plasma concentrations of clozapine and its major metabolites, norclozapine and clozapine-N-oxide, have been controversial. Since the frequency distribution of the plasma levels is asymmetrical and skewed to the right, the statistical methods (such as analysis of variance and regression analysis) used earlier are actually inappropriate for analyzing the effects of the variables on the concentrations and might contribute to the inconsistent results. The goal of the present study, with befitting statistics, is to measure the potential effect of dose, gender, age, and body weight on plasma levels of clozapine and its 2 major metabolites. Method: We retrospectively analyzed data from a therapeutic drug monitoring study for steady-state plasma clozapine, norclozapine, and clozapine-N-oxide levels that was conducted in a large group of Chinese schizophrenic inpatients (male:female ratio = 83:79; age range, 33.8 +/- 9.3 years). The daily doses of clozapine had ranged from 100 to 900 mg, with a mean +/- SD value of 379.5 +/- 142.2 mg, Plasma concentrations had been measured using highperformance liquid chromatography with ultraviolet detection. Multiple linear regression was adopted to quantify the effects of various factors on the plasma levels. The natural logarithm of the plasma level was used as the dependent variable to overcome the skewness problem. Results: After adjusting the effects of gender, age, and body weight by multiple linear regression, each l-mg increment in the daily dose could raisethe clozapine level by 0.31%, norclozapine by 0.27%, and clozapine-N-oxideby 0.16%. Female patients had 34.9% higher clozapine levels and 36.3% higher norclozapine, with other variables being controlled. No sex differences were demonstrated for clozapine-N-oxide levels. Each 1-year increment in age would elevate the clozapine level by 1.1%, norclozapine by 1.0%, and clozapine-N-oxide by 1.0%. Body weight could not influence the levels of these compounds. Conclusion: The present results suggest that women possess higher plasma levels (about one third higher) of clozapine and norclozapine, but not the N-oxide metabolite. Each addition of 1 year in age elevated clozapine and either metabolite's levels by about 1%. Furthermore, every l-mg increase in the daily dose raised clozapine and norclozapine concentrations by approximately 0.3%. These findings could assist clinicians in optimizing clozapine dosing strategies.

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Documento generato il 20/01/20 alle ore 16:01:39