氯氮平暴露和吸烟和性别的影响:人口药代动力学研究。

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Ng W,田H,伊斯梅尔Z,乳房,Rajji TK,雷明顿G, Sproule B,波洛克BG, Mulsant BH, bie RR

氯氮平暴露和吸烟和性别的影响:人口药代动力学研究。

药物Monit。2009年6月,31 (3):360 - 6。doi: 10.1097 / FTD.0b013e31819c7037。

PubMed ID

19349931 (在PubMed

]

文摘

本研究的主要目的是评估暴露于氯氮平浓度的大小和可变性和norclozapine在实际的临床中,关注吸烟状态、使用人口药代动力学方法。血浆氯氮平的回顾性研究和norclozapine浓度从住院病人成瘾与精神健康中心,多伦多,从2001年到2007年。使用NONMEM非线性mixed-effects模型开发,包括年龄、性别、体重、吸烟状况、和剂量配方不。药代动力学参数估计和个人间残留可变性和1 - 2-compartment模型。519从197例患者血浆氯氮平浓度(138男性;意思是+ / - SD年龄38 + / - 13年;精神分裂症谱系障碍98.2%)包括分析。1-compartment模型与一阶吸收和消除最好的描述数据。表观分布容积是固定之前报道的文学价值7 L /公斤。population-predicted口服氯氮平的间隙和norclozapine 18.0和39.0 L / h,分别; both the predicted clearance values vary nearly 6-fold (range, 9.18-59.06 and 16.29-97.84 L/h, respectively). For clozapine, smokers and males showed increased oral clearance by 6.0 and 4.5 L/h, respectively. For norclozapine, smokers and male gender were associated with an increased oral clearance of 11.3 and 7.6 L/h, respectively. The formulation of clozapine administered had an impact on the absorption rate with a Ka of 0.14/h for tablet and 10.3/h for the suspension form.The data suggest that smoking and male gender are associated with lower exposure to clozapine and norclozapine due to the higher oral clearance. These findings may account for some of the variability in clozapine exposure and have important implications for individualized drug dosing and therapeutic drug monitoring.

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药物

氯氮平