Pharmacokinetic Modeling and Prediction of Plasma Pyrrole-Imidazole Polyamide Concentration in Rats Using Simultaneous Urinary and Biliary Excretion Data
Pharmacokinetic Modeling and Prediction of Plasma Pyrrole-Imidazole Polyamide Concentration in Rats Using Simultaneous Urinary and Biliary Excretion Data
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DOI：
10.1248/bpb.32.921
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发表时间：
2009-05-01
影响因子：
2
通讯作者：
Matsumoto, Yoshiaki
中科院分区：
文献类型：
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作者：
Nagashima, Takashi;Aoyama, Takahiko;Matsumoto, Yoshiaki
如果生物分析方法缺乏适当的灵敏度来充分表征血清或血浆浓度-时间曲线，则认为使用尿液和/或胆汁排泄数据是一种替代方法。该方法用于分析各种分析仪器定量下限（LLOQ）下的血药浓度-时间曲线。本研究的目的是开发药代动力学（PK）模型，该模型使用尿液和胆汁排泄数据描述HPLC LLOQ下的血浆浓度-时间曲线。作为模型化合物，使用吡咯（Py）-咪唑（Im）聚酰胺1035（MW，1035.12）和1666（MW，1665.78）。Py-Im聚酰胺1035和1666的累积尿排泄量分别为给药剂量的72.4 +/- 11.6和4.8 +/- 0.5%。Py-Im聚酰胺1035的累积胆汁排泄量为给药剂量的4.3 ± 0.4%，未检测到Py-Im聚酰胺1666。使用线性和非线性输出室充分描述了Py-Im聚酰胺1035的血浆浓度-时间曲线。开发的PK模型可用于描述血浆浓度曲线，其中线性输出隔室解释为尿液隔室，非线性输出隔室解释为胆汁隔室。该PK模型将能够更准确地预测LLOQ下的血药浓度曲线。
The use of urinary and/or biliary excretion data was considered as an alternative approach if the bioanalytical method lacked the appropriate sensitivity to adequately characterize the serum or plasma concentration-time profile. This approach is used for the analysis of plasma concentration-time profile under the lower limit of quantification (LLOQ) of various analytical instruments. The objective of this study was to develop a pharmacokinetic (PK) model that describes the plasma concentration-time profiles under LLOQ of HPLC using urinary and biliary excretion data. As model compounds, pyrrole (Py)-imidazole (Im) polyamides 1035 (MW, 1035.12) and 1666 (MW, 1665.78) were used. The cumulative urinary excretions of Py-Im polyamides 1035 and 1666 were 72.4 +/- 11.6 and 4.8 +/- 0.5% of the administered dose, respectively. The cumulative biliary excretion of Py-Im polyamide 1035 was 4.3 +/- 0.4% of the administered dose, and Py-Im polyamide 1666 was not detected. The plasma concentration-time profiles of Py-Im polyamide 1035 were adequately described using linear and non-linear output compartments. The developed PK model could he used to describe the plasma concentration profiles using the linear output compartment interpreted as the urine compartment and the non-linear output compartment interpreted as the bile compartment. This PK model will be able to provide a more Accurate prediction of the plasma concentration profiles under LLOQ.