Krishnaswamy K, Ushasri V, Naidu N A
Clin Pharmacokinet. 1981 Mar-Apr;6(2):152-9. doi: 10.2165/00003088-198106020-00005.
The pharmacokinetics of phenylbutazone were studied after a single oral dose of 6 mg/kg bodyweight in 35 adult male subjects with differing nutritional status. The elimination half-life was significantly shorter and plasma clearance accelerated in undernourished patients who had significant weight deficit and low serum albumin concentration. Plasma protein binding was only 86% compared with 95 to 96% in normal subjects (smokers and non-smokers). The apparent volume of distribution was also higher in undernourished patients. Significant correlations were observed between serum albumin, protein binding and bodyweight. Multiple regression analysis of the data indicated that altered drug protein binding partially contributed towards variation in half-life and clearance; and the plasma albumin concentration significantly influenced the amount of drug bound in plasma. The results indicate that nutritional status is one of the important environmental variables that can alter drug kinetics and disposition in man. Further studies, including measurement of steady-state plasma concentrations of various other drugs, are necessary to elucidate drug kinetics in malnourished subjects.
在35名营养状况各异的成年男性受试者中，单次口服6mg/kg体重的苯基布他松后，对其药代动力学进行了研究。在体重明显不足且血清白蛋白浓度较低的营养不良患者中，消除半衰期显著缩短，血浆清除率加快。血浆蛋白结合率仅为86%，而正常受试者（吸烟者和非吸烟者）为95%至96%。营养不良患者的表观分布容积也更高。血清白蛋白、蛋白结合率与体重之间存在显著相关性。对数据进行多元回归分析表明，药物蛋白结合的改变部分导致了半衰期和清除率的变化；血浆白蛋白浓度显著影响血浆中结合的药物量。结果表明，营养状况是可改变人体药物动力学和处置的重要环境变量之一。有必要进行进一步研究，包括测定其他各种药物的稳态血浆浓度，以阐明营养不良受试者的药物动力学。
