Mouankie J B, Senczuk W, Florek E
Faculty of Pharmacy, Poznan University of Medical Sciences, Poznan, Poland.
Eur J Drug Metab Pharmacokinet. 2009 Jul-Sep;34(3-4):173-6. doi: 10.1007/BF03191170.
A pharmacokinetic study of pyrimethamine was carried out in 4- (103-115 g) and 12-week-old (260-280 g) white male Wistar rats fed a standard diet containing 24% protein, and a low-protein diet containing 8% protein. After intragastric administration of the drug in a single dose of 40 mg/kg body weight, the concentrations of pyrimethamine in the blood were determined at different time points from 15 min to 20 hours post-dose. On the basis of the results obtained, a number of parameters characterizing the course of absorption and elimination of the drug from the blood were calculated. The majority of parameters were dependent on both age and type of diet. The greatest bioavailability was observed in the 4-week-old rats: for the animals fed the low-protein diet, the area under the concentration-time curve (AUC) amounted to 593.0 and for those on the standard diet the AUC was 503.1. In the older rats, this parameter was 339.3 and 228.1 respectively. The k(e) values were lower in the younger rats (i.e. 0.0121 h(-1) and 0.0135 h(-1)) than in the older animals (i.e. 0.0164 h(-1) and 0.0193 h(-1) respectively). The elimination half-life (t1/2) was higher in the 4-week-old rats (i.e. 57.1 h; 8% protein, and 51.2 h; 24% protein) than in the 12-week-old animals (i.e. 42.4 h; 8% protein, and 36.0 h; 24% protein).
对4周龄（103 - 115克）和12周龄（260 - 280克）的雄性白色Wistar大鼠进行了乙胺嘧啶的药代动力学研究，这些大鼠分别喂食含24%蛋白质的标准饮食和含8%蛋白质的低蛋白饮食。以40毫克/千克体重的单剂量对大鼠进行胃内给药后，在给药后15分钟至20小时的不同时间点测定血液中乙胺嘧啶的浓度。根据所得结果，计算了一些表征药物从血液中吸收和消除过程的参数。大多数参数既取决于年龄，也取决于饮食类型。在4周龄大鼠中观察到最大的生物利用度：对于喂食低蛋白饮食的动物，浓度 - 时间曲线下面积（AUC）为593.0，对于喂食标准饮食的动物，AUC为503.1。在年龄较大的大鼠中，该参数分别为339.3和228.1。年轻大鼠的k(e)值（即0.0121 h⁻¹和0.0135 h⁻¹）低于年龄较大的动物（即分别为0.0164 h⁻¹和0.0193 h⁻¹）。4周龄大鼠的消除半衰期（t1/2）（即57.1小时；8%蛋白质，和51.2小时；24%蛋白质）高于12周龄动物（即42.4小时；8%蛋白质，和36.0小时；24%蛋白质）。
