Boudinot S G, Funderburg E D, Boudinot F D
Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens 30602.
J Pharm Sci. 1993 Mar;82(3):254-7. doi: 10.1002/jps.2600820307.
This study examined the effects of age on the pharmacokinetics of piroxicam in rats. Two groups of rats, aged 5 and 24 months, were administered 1 mg of piroxicam per kg intravenously, and blood samples were withdrawn for up to 120 h. Protein binding studies, with pooled serum from each age group were also performed. Piroxicam concentrations were determined by HPLC analysis, and pharmacokinetic parameters were characterized by area-moment analysis. Plasma piroxicam concentrations declined in both age groups in a biexponential fashion, with half-lives of 5.9 +/- 0.7 h (mean +/- SD) in the young rats and 30.6 +/- 9.9 h in the old rats. Total clearance in the young rats was 0.048 +/- 0.012 L/h/kg, whereas that in the old rats was 0.021 +/- 0.003 L/h/kg. The steady-state volume of distribution in the young rats was 0.42 +/- 0.05 L/kg, and that in the old rats was 0.56 +/- 0.10 L/kg. There was a statistically significant difference between these parameters calculated for each age group. Piroxicam is a highly plasma protein-bound drug; the fraction unbound in the young rats was determined to be 0.067 +/- 0.022, and that in the old rats was determined to be 0.134 +/- 0.065, or twice that in the young rats. Differences in protein binding were due, in part, to a 20% decreased albumin concentration in the old rats; however, there was also a decrease in the number of binding sites and/or the binding affinity with aging.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究考察了年龄对吡罗昔康在大鼠体内药代动力学的影响。将两组分别为5月龄和24月龄的大鼠静脉注射1 mg/kg的吡罗昔康，并在长达120小时内采集血样。还采用各年龄组的混合血清进行了蛋白结合研究。通过高效液相色谱分析测定吡罗昔康浓度，并采用面积矩分析法表征药代动力学参数。两个年龄组的血浆吡罗昔康浓度均呈双指数下降，幼鼠的半衰期为5.9±0.7小时（均值±标准差），老龄鼠为30.6±9.9小时。幼鼠的总清除率为0.048±0.012 L/h/kg，而老龄鼠为0.021±0.003 L/h/kg。幼鼠的稳态分布容积为0.42±0.05 L/kg，老龄鼠为0.56±0.10 L/kg。各年龄组计算得到的这些参数之间存在统计学显著差异。吡罗昔康是一种血浆蛋白高度结合的药物；幼鼠中未结合部分测定为0.067±0.022，老龄鼠中为0.134±0.065，是幼鼠的两倍。蛋白结合的差异部分归因于老龄鼠白蛋白浓度降低20%；然而，随着年龄增长，结合位点数量和/或结合亲和力也有所下降。（摘要截断于250字）
