Keller F, Maiga M, Neumayer H H, Lode H, Distler A
Eur J Drug Metab Pharmacokinet. 1984 Jul-Sep;9(3):275-82. doi: 10.1007/BF03189651.
The measurement of plasma drug concentrations provides no insight into the relationship between the free and the plasma-protein-bound fractions of drugs. Plasma protein binding may decrease in renal disease due to uremia, hypoalbuminemia, or due to drug interactions. Decreased plasma protein binding leads to an increase in free plasma fraction causing an increase in volume of distribution and a shorter elimination half life. The increase in the apparent volume of distribution and the shorter elimination half life cause a decrease in total plasma concentration. Therefore, the free drug concentration is more reliable than the total plasma concentration for therapeutic drug monitoring. However, the free amount in plasma and in tissue and the tissue-bound amount remain unchanged under steady state conditions. Thus, a decrease in plasma protein binding in renal disease usually does not lead to increased drug toxicity, and alteration of drug dosage is not required, although the total plasma concentration may be found to be considerably lower than normal. In addition to plasma protein binding, alteration of tissue binding must also be considered for the determination of the appropriate dosage of some drugs in renal disease.
血浆药物浓度的测定无法揭示药物游离部分与血浆蛋白结合部分之间的关系。由于尿毒症、低白蛋白血症或药物相互作用，肾脏疾病时血浆蛋白结合可能会降低。血浆蛋白结合减少会导致游离血浆部分增加，从而使分布容积增加，消除半衰期缩短。分布容积增加和消除半衰期缩短会导致血浆总浓度降低。因此，对于治疗药物监测而言，游离药物浓度比血浆总浓度更可靠。然而，在稳态条件下，血浆和组织中的游离量以及组织结合量保持不变。因此，肾脏疾病时血浆蛋白结合减少通常不会导致药物毒性增加，尽管血浆总浓度可能会显著低于正常水平，但并不需要改变药物剂量。除了血浆蛋白结合外，在确定肾脏疾病时某些药物的合适剂量时，还必须考虑组织结合的改变。
