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[非胰岛素依赖型糖尿病患者阿米卡星药代动力学参数的非参数估计]

[Non-parametric estimation of pharmacokinetic parameters of amikacin in patients with non-insulin-dependent diabetes mellitus].

作者信息

Corvaisier S, Bleyzac N, Confesson M A, Bureau C, Maire P

机构信息

ADCAPT, Service Pharmaceutique, Hôpital A. Charial, Hospices Civils de Lyon, Francheville, France.

出版信息

Therapie. 1997 May-Jun;52(3):219-26.

PMID:9366106
Abstract

To establish a reference for MAP Bayesian adaptive control of amikacin therapy in non-insulin-dependent diabetic patients, 30 patients (age: 63.5 +/- 10.1 years) were studied. Weight (84.2 +/- 15.4 kg) and body mass index (28.0 +/- 4.3 kg/m2 for males and 30.5 +/- 6.4 kg/m2 for females) were stable during treatment. Creatinine clearance (CCr) was 70.3 +/- 27.2 ml/min/1.73 m2 before treatment and 69.6 +/- 24.3 ml/min/1.73 m2 (NS) at the end of treatment (2 to 15 days). 129 serum concentrations were drawn (4.8 +/- 2.6 levels per patient). The one-compartment model was parameterized as having Vs (l.kg-1) and Kslope (min/ml.h) for each unit of CCr (Kel = Kintercept + Kslope x CCr). The non-renal Kintercept was fixed at 0.00693 h-1. The NPEM computes the joint probability densities. The mean, median, and SD were respectively: Vs = 0.3574, 0.3654, 0.0825 l.kg-1; Kslope = 0.0026, 0.0027, 0.0007 min/ml.h. For the a priori first doses determination, precision is higher with the new population. No difference in adaptive control was observed. In additive, the full joint density probability should be used to develop stochastic multiple model linear quadratic (MMLQ) adaptive control strategies.

摘要

为建立非胰岛素依赖型糖尿病患者阿米卡星治疗的MAP贝叶斯自适应控制的参考标准,对30例患者(年龄:63.5±10.1岁)进行了研究。治疗期间体重(84.2±15.4kg)和体重指数(男性为28.0±4.3kg/m²,女性为30.5±6.4kg/m²)保持稳定。治疗前肌酐清除率(CCr)为70.3±27.2ml/min/1.73m²,治疗结束时(2至15天)为69.6±24.3ml/min/1.73m²(无显著性差异)。采集了129份血清浓度样本(每位患者4.8±2.6个浓度水平)。单室模型参数化为每个CCr单位具有Vs(l.kg⁻¹)和Kslope(min/ml.h)(Kel = Kintercept + Kslope×CCr)。非肾性Kintercept固定为0.00693h⁻¹。NPEM计算联合概率密度。均值、中位数和标准差分别为:Vs = 0.3574、0.3654、0.0825l.kg⁻¹;Kslope = 0.0026、0.0027、0.0007min/ml.h。对于先验首次剂量的确定,新群体的精度更高。未观察到自适应控制方面的差异。此外,应使用完整的联合密度概率来制定随机多模型线性二次(MMLQ)自适应控制策略。

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