Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

Abstract

Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore, there may be a failure to maintain homeostasis under conditions of physiolog ical stress. The reduced homeostatic ability affects different regulatory systems in different subjects, thus explaining at least partly the increased interindividual variability occurring as people get older. Important pharmacokinetic and pharmacodynamic changes occur with advancing age. Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life) whereas pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs. This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.

Human chorionic gonadotropin (hCG) plasma levels at oocyte retrieval and IVF outcomes

“…A number of age-related changes in pharmacokinetics and pharmacodynamics have been reported in studies mainly focusing on elderly people [23]. The majority of such changes lead to higher drug concentrations [23].…”

“…A number of age-related changes in pharmacokinetics and pharmacodynamics have been reported in studies mainly focusing on elderly people [23]. The majority of such changes lead to higher drug concentrations [23]. There is also, however, a progressive reduction in total body water with an increase in plasma volume, and a decrease in lean body mass, resulting in a relative increase in body fat, especially in women [24].…”

Population Pharmacokinetic/Pharmacodynamic Modeling of Depot Testosterone Cypionate in Healthy Male Subjects

“…Re‐estimation of the PK parameters may be necessary if the current PPK model is going to be applied to the patient population. A series of physiological changes in renal function, body composition, or protein concentrations is likely to affect the binding affinity of testosterone as well as the PK profile of exogenous testosterone administration in the elderly patients 26, 27. Certain patient populations may also have lower levels of endogenous testosterone secretion, and altered ${\beta }_{base}$ compared with our model estimates.…”

Antimicrobial Distribution From Local Delivery Depends on Dose

“…Our study documented concentrations near the depot that were near the target levels or greater for only a few weeks, even when a highdose formulation, 10 g Gd-DTPA per batch or greater, is used. The relatively short duration of high levels in tissue may be due to clearance Gd-DTPA occurring faster than it is being released after a few weeks [20]. Our data are consistent with the data of Adams et al [1], who showed that antimicrobial concentrations dropped below the break point sensitivity limit (* 1-8 lg/mL, different for each antimicrobial) after 9 to 14 days of release from bone cement with 6 to 9 g antimicrobial per 40-g batch.…”