Biological determinants of altered pharmacokinetics in the elderly

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.