PHARMACOKINETICS OF TRIMETHOPRIM IN THE RAT
PHARMACOKINETICS OF TRIMETHOPRIM IN THE RAT
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DOI：
10.1002/jps.2600780709
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发表时间：
1989-07-01
影响因子：
3.8
通讯作者：
ALBERS, DD
中科院分区：
文献类型：
--
作者：
TU, YH;ALLEN, LV;ALBERS, DD
在雄性Sprague-Dawley大鼠中研究了以25 mg/kg剂量静脉内给予甲氧苄啶后甲氧苄啶的药代动力学。通过反相高效液相色谱法测定甲氧苄啶的血浆和组织水平，作为时间的函数。甲氧苄啶的处置描述了两个开放的二室模型，从中央室和非房室方法消除。对于房室分析，终末消除速率常数、中央室的消除半衰期表观分布容积、基于血药浓度-时间曲线下面积的中央室表观分布容积和稳态分布容积分别为0.007 min-1、99 min、2059 mL/kg、5729 mL/kg，和2473 mL/kg。采用统计矩理论计算非房室模型药动学参数。甲氧苄啶稳态时的平均停留时间、清除率和分布容积的估计值计算为52 min，40 mL. cm。min-1 kg-1，2097 mL.甲氧苄啶的组织分布遵循双相现象，在心、肺、脾、肝、肾、精囊和肌肉中的最大浓度为30 min，在睾丸中的最大浓度为45 min，在前列腺中的最大浓度为20 min，在脑中的最大浓度为7 L 10 min。数据显示，与血浆浓度相比，在心脏、睾丸、脾脏、肝脏、肾脏、前列腺和精囊中发现较高水平的甲氧苄啶;在肌肉中发现类似浓度，但在大脑和睾丸中发现较低水平的甲氧苄啶。
The pharmacokinetics of trimethoprim was studied in male Sprague-Dawley rats following the intravenous administration of trimethoprim at a dose of 25 mg/kg. Plasma and tissue levels of trimethoprim, as a function of time, were determined by reversed-phase high-performance liquid chromatography. The disposition of trimethoprim was described by both a two-compartment open model with elimination from a central compartment and a noncompartmental method. For the compartmental analysis, the terminal elimination rate constant, elimination half-life apparent volume of distribution in the central compartment, apparent volume of distribution in the central comparment based on the area under the plasma concentration-time curve, and volume of distribution at steady state, were determined to be 0.007 min-1, 99 min, 2059 mL/kg, 5729 mL/kg, and 2473 mL/kg, respectively. Noncompartmental pharmacokinetic parameters were obtained by the statistical moment theory. The estimates for mean residence time, clearance, and volume of distribution at steady state of trimethoprim were calculated to be 52 min, 40 mL .cntdot. min-1 kg-1, and 2097 mL, respectively. Tissue distribution of trimethoprim followed a biphasic phenomenon with a maximum concentration at 30 min for heart, lung spleen, liver, kidney, seminal vesicles, and muscle, and at 45 min for testicles, 20 min for prostate gland, and 7L 10 min for brain. The data show that compared with the plasma cocnentration, higher levels of trimethoprim were found in heart, lng, spleen, liver, kidney, prostate gland, and semial vesicles; a similar concentration was found for muscle, but lower levels of trimethoprim were found for brain and testicles.