A population pharmacokinetic model of trimethoprim in patients with pneumocystis pneumonia, made with parametric and nonparametric methods
A population pharmacokinetic model of trimethoprim in patients with pneumocystis pneumonia, made with parametric and nonparametric methods
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DOI：
10.1097/00007691-199708000-00015
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发表时间：
1997-08-01
影响因子：
2.5
通讯作者：
Sattler, FR
中科院分区：
文献类型：
--
作者：
Jelliffe, RW;Gomis, P;Sattler, FR
应用参数迭代两阶段贝叶斯和非参数期望最大化计算机程序，建立了获得性免疫缺陷综合征和卡氏肺孢子虫肺炎患者静脉和口服甲氧普林的群体药代动力学模型。当血清水平数据中存在良好信息时，两种方法得到相似的结果。经非参数期望最大化程序计算，吸收速率常数Ka的中位数为1.602小时(-1)，肌酐清除与消除关系的斜率中位数Ks为0.001168小时(-1)，表观分布体积的中位数(Vs)为1.058 L/kg，口服吸收剂量的中位数(Fa)为0.955。这些结果允许根据体重和肾功能调整剂量个体化，以实现选定的血清水平峰值和谷值目标。对于这一人群中的大多数患者来说，9ug/ml的峰值目标和5ug/ml的低谷目标似乎是合理的，应该允许大多数患者完成一个有效的疗程，同时降低治疗风险-终止血液毒性。然而，治疗目标的选择应始终基于每个患者对药物的明显需求以及为获得药物的预期益处而合理接受的毒性风险。
A population pharmacokinetic model of intravenously and orally administered trimethoprim in patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia has been made using a parametric iterative two-stage Bayesian and a nonparametric expectation maximization computer program. When good information was present in the serum level data, both methods obtained similar results. With the nonparametric expectation maximization program, the median apparent rate constant for absorption (Ka) was 1.602 hr(-1), median slope (Ks) of the relationship between creatinine clearance and elimination was 0.001168 hr(-1), median apparent volume of distribution (Vs) was 1.058 l/kg, and median fraction of oral dose absorbed (Fa) was 0.955. These results permit dosage individualization adjusted to body weight and renal function to achieve chosen serum level peak and trough goals. Peak goals of 9 ug/ml and trough goals of 5 ug/ml appear reasonable for most patients in this population, and should permit most to complete an effective course of therapy with a reduced risk for treatment-terminating hematologic toxicity. However, therapeutic goals should always be selected based on each patient's apparent need for the drug and the risk of toxicity that is justifiably acceptable to obtain the expected benefits of the drug.