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首页> 外文期刊>Primary care companion to the journal of clinical psychiatry >Quantifying Intraindividual Variations in Plasma Clozapine Levels: A Population Pharmacokinetic Approach
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Quantifying Intraindividual Variations in Plasma Clozapine Levels: A Population Pharmacokinetic Approach

机译：定量血浆氯氮平水平的intraindividual变化：人口药代动力学方法。

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Objective: Clozapine has strong recommendations for therapeutic drug monitoring. While factors that influence interindividual variation in plasma clozapine levels have been extensively reported, intraindividual variation remains poorly studied. We employed a population pharmacokinetic approach to assess intraindividual variations in plasma levels of both clozapine and N-desmethylclozapine, as well as the impact of smoking on this variability. Methods: Patients who were initiated on clozapine from January 2009 to December 2010 and who provided at least 2 plasma samples were included in this study. The observed concentrations of clozapine and N-desmethylclozapine were applied in a Bayesian pharmacokinetic modeling approach by using a previously published pharmacokinetic model from an independent sample to compute a predicted concentration. The predicted concentrations of clozapine and N-desmethylclozapine were then compared with the observed concentrations in the form of a ratio: predicted-to-observed concentration ratio (Cpred/Cobs). The coefficient of variation of the Cpred/Cobs ratios was taken as a measure of intraindividual variation. Results: A total of 723 plasma levels from 61 patients were included in this analysis. The coefficient of variation of Cpred/Cobs ratios for clozapine and N-desmethylclozapine were 29.8% (SD = 17.2%) and 27.4% (SD = 16.4%), respectively. Though values were higher, smoking did not have a significant effect on coefficients of variation of clozapine (33.5% vs 26.3%, P = .184) or N-desmethylclozapine (30.7% vs 24.2%, P = .100). Conclusions: Clinicians need to be aware of intraindividual variability and not assume that plasma levels are static. If plasma levels are used to guide dosing of clozapine, serial measurements rather than a single level might be necessary to make an informed clinical decision. The clinical implications of intraindividual variability in plasma clozapine levels need further study.
机译：目的：氯氮平对治疗药物监测有强烈建议。尽管已经广泛报道了影响血浆氯氮平水平个体间差异的因素，但对个体间差异的研究仍很少。我们采用了群体药代动力学方法来评估氯氮平和N-去甲基氯氮平的血浆水平的个体差异以及吸烟对这种变异性的影响。方法：本研究包括从2009年1月至2010年12月开始接受氯氮平治疗并提供至少2份血浆样品的患者。观察到的氯氮平和N-去甲基氯氮平的浓度通过使用先前发表的来自独立样品的药代动力学模型以贝叶斯药代动力学建模方法来计算预测浓度。然后将氯氮平和N-去甲基氯氮平的预测浓度与观察到的浓度以比率的形式进行比较：预测与观察到的浓度比（Cpred / Cobs）。 Cpred / Cobs比率的变异系数被视为个体差异的量度。结果：这项分析共纳入了来自61例患者的723种血浆水平。氯氮平和N-去甲基氯氮平的Cpred / Cobs比的变异系数分别为29.8％（SD = 17.2％）和27.4％（SD = 16.4％）。尽管该值较高，但吸烟对氯氮平（33.5％vs 26.3％，P = .184）或N-去甲基氯氮平（30.7％vs 24.2％，P = .100）的变异系数没有显着影响。结论：临床医生需要意识到个体间的变异性，而不应假设血浆水平是静态的。如果使用血浆水平指导氯氮平的剂量，则可能需要进行串行测量而不是单一水平才能做出明智的临床决策。血浆氯氮平水平的个体差异的临床意义需要进一步研究。

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