Shand D G
Gerontology. 1982;28 Suppl 1:8-17. doi: 10.1159/000212568.
The biological determinants of drug disposition have been clearly identified and methods are available to quantify what effects altering them will have on drug kinetics. The factors include blood flow and intrinsic clearance of the organ of elimination, drug binding in blood and tissues, and, in the case of drugs eliminated by the liver, the oral route of administration. The effects of these various factors on drug elimination depend on the efficiency of the elimination process. At one end of the spectrum, some drug elimination is very efficient as it is largely flow-dependent, while at the other elimination depends largely on intrinsic clearance. The oral route of elimination may be important for drugs which undergo efficient hepatic extraction, when a large "first-pass" effect results. In addition, that fraction of the drug escaping first-pass elimination is largely dependent on intrinsic clearance and not flow. Finally, plasma drug binding may affect both elimination and drug distribution. The way in which these factors can be affected by the aging process will be discussed and illustrated with examples showing how changes in organ blood flow, intrinsic clearance and plasma drug binding can produce pharmacokinetic changes seen in the elderly.
药物处置的生物学决定因素已被明确识别，并且有方法可用于量化改变这些因素对药物动力学的影响。这些因素包括消除器官的血流和内在清除率、药物在血液和组织中的结合，以及对于经肝脏消除的药物而言的口服给药途径。这些不同因素对药物消除的影响取决于消除过程的效率。在一个极端情况下，一些药物消除非常高效，因为它很大程度上依赖于血流，而在另一个极端情况下，消除很大程度上取决于内在清除率。当产生较大的“首过”效应时，口服消除途径对于那些经历高效肝脏提取的药物可能很重要。此外，逃过首过消除的那部分药物很大程度上取决于内在清除率而非血流。最后，血浆药物结合可能会影响消除和药物分布。将讨论这些因素如何受到衰老过程的影响，并举例说明器官血流、内在清除率和血浆药物结合的变化如何导致在老年人中观察到的药代动力学变化。
