Therapeutic drug monitoring of olanzapine: The combined effect of age, gender, smoking, and comedication
Therapeutic drug monitoring of olanzapine: The combined effect of age, gender, smoking, and comedication
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DOI：
10.1097/00007691-200302000-00007
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发表时间：
2003-02-01
影响因子：
2.5
通讯作者：
Balant, LP
中科院分区：
文献类型：
--
作者：
Gex-Fabry, M;Balant-Gorgia, AE;Balant, LP
研究了抗精神病药物奥氮平的治疗药物监测（TDM）数据，包括浓度与剂量关系、个体内与个体间变异性以及患者特征对稳态浓度的综合影响。该研究包括250名患者，每日剂量从2.5毫克到30毫克不等。中位浓度剂量比为2.1 (ng/mL)/(mg/d)， 90%分布在5倍范围内。在第一个亚组中，患者在不同剂量下进行两次测量（n = 21），数据符合浓度与剂量的线性关系。在第二组患者中，以固定日剂量重复测量（n = 40），患者内部和患者之间的变异性估计分别为30.5%和49.4%。在整个样本中，剂量标准化浓度的多元回归分析显示，给药后时间（每12小时延迟-18%，P < 0.05）、年龄大于或等于60岁（+27%,P < 0.005）、吸烟（-12%,P < 0.05）、氟伏沙明（+74%,P < 0.001）、帕罗西汀、氟西汀或舍曲林（一起考虑，+32%,P < 0.05）、文拉法辛（+27%,P < 0.05）和P450酶诱诱剂（-40%,P < 0.001）均有显著影响。最终模型包括与女性性别相关的较高浓度趋势（+11%,P = 0.07），占观察到的个体间变异性的27%。当考虑到最坏的情况时，服用氟伏沙明的老年非吸烟女性的奥氮平浓度预计比服用卡马西平的年轻男性高4.6倍。目前的研究表明，以代谢改变相关因素组合为特征的患者可能受益于奥氮平TDM。
Therapeutic drug monitoring (TDM) data for the antipsychotic drug olanzapine were investigated with respect to concentration versus dose relationship, intra-individual versus interindividual variability, and the combined influence of patient characteristics on steady-state concentration. The study included 250 patients, with daily doses ranging from 2.5 to 30 mg. Median concentration to dose ratio was 2.1 (ng/mL)/(mg/d), with 90% of the distribution in a fivefold range. In the first subgroup of patients with two measurements at different doses (n = 21), data were in keeping with linear concentration versus dose relationship. In the second subgroup of patients with repeated measurements at a constant daily dose (n = 40), estimates of within-patient and between-patient variabilities were 30.5% and 49.4%, respectively. In the whole sample, multiple regression analysis of dose-normalized concentration revealed significant effects of time postdose (-18% per 12 hours delay, P < 0.05), age greater than or equal to 60 years (+27%, P < 0.005), cigarette smoking (-12%, P < 0.05), and comedication with fluvoxamine (+74%, P < 0.001), paroxetine, fluoxetine, or sertraline (considered together, +32%, P < 0.05), venlafaxine (+27%, P < 0.05), and inducers of P450 enzymes (-40%, P < 0.001). The final model included a tendency for higher concentration associated with female gender (+11%, P = 0.07) and accounted for 27% of observed interindividual variability. When considering a worst-case scenario, an elderly, nonsmoking woman prescribed fluvoxamine comedication was predicted to reach a 4.6-fold higher olanzapine concentration than a young male smoker coadministered carbamazepine. The current study suggests that patients characterized by a combination of factors associated with altered metabolism may benefit from olanzapine TDM.