Clinical Pharmacology in the Older Adult

Abstract

Drug pharmacokinetics are influenced by a number of patient-specific factors, including age. Interindividual variability in physiology increases with age, making it necessary to consider the patient’s overall condition, “physiologic age,” disease states, and concurrent medications when applying general knowledge of pharmacokinetic differences in older adults to the care of individual patients. Geriatric patients may demonstrate altered bioavailability, absorption, distribution, metabolism, and renal excretion of drugs. Most clinically significant pharmacokinetic changes in advanced age can be attributed to altered renal and hepatic metabolic function. The prevalence of cancer among older adults is high and increasing, resulting in increasing exposure to chemotherapeutic agents in geriatric patients. Overall, age-related renal impairment is the major cause of dose modifications for chemotherapeutic agents in older adults, and the (estimated) creatinine clearance (CLcr by the Cockcroft–Gault method) serves as a good predictor for a patient-individualized dosing regimen. Apparent age-related effects on hepatic drug metabolism/biliary excretion have been observed, but usually do not lead to dose adjustments; however, metabolic drug–drug interactions (i.e., inhibition or induction of drug metabolizing enzymes or drug transporters in the liver and/or GI tract) can be very important in older adults, as they are more likely to receive comedications for diseases unrelated to their cancer with the potential for drug–drug interactions. Recommended dosage adjustments for select chemotherapeutic agents are summarized in this chapter.