Overview of Pharmacokinetics

Pharmacokinetics, sometimes described as what the body does to a drug, refers to the movement of drug into, through, and out of the body—the time course of its absorption, bioavailability, distribution, metabolism, and excretion.

Pharmacodynamics, described as what a drug does to the body, involves receptor binding, postreceptor effects, and chemical interactions.

Drug pharmacokinetics determines the onset, duration, and intensity of a drug’s effect. Formulas relating these processes summarize the pharmacokinetic behavior of most drugs (see table Formulas Defining Basic Pharmacokinetic Parameters).

Pharmacokinetics of a drug depends on patient-related factors as well as on the drug’s chemical properties. Some patient-related factors (eg, renal function, genetic makeup, sex, age) can be used to predict the pharmacokinetic parameters in populations. For example, the half-life of some drugs, especially those that require both metabolism and excretion, may be remarkably long in older adults (see figure Comparison of Pharmacokinetic Outcomes for Diazepam in a Younger Man [A] and an Older Man [B]). In fact, physiologic changes with aging affect many aspects of pharmacokinetics (see Pharmacokinetics in Older Adults and Pharmacokinetics in Children) (1, 2).

Other factors are related to individual physiology. The effects of some individual factors (eg, renal failure, obesity, hepatic failure, dehydration) can be reasonably predicted, but other factors are idiosyncratic and thus have unpredictable effects. Because of individual differences, drug administration must be based on each patient’s needs—traditionally, by empirically adjusting dosage until the therapeutic objective is met. This approach is frequently inadequate because it can delay optimal response or result in adverse effects.

Knowledge of pharmacokinetic principles helps prescribers adjust dosage more accurately and rapidly. Application of pharmacokinetic principles to individualize pharmacotherapy is termed therapeutic drug monitoring.

Comparison of Pharmacokinetic Outcomes for Diazepam in a Younger Man (A) and an Older Man (B)

Diazepam is metabolized in the liver to desmethyldiazepam through P-450 enzymes. Desmethyldiazepam is an active sedative, which is excreted by the kidneys. 0 = time of dosing. (Adapted from Greenblatt DJ, Allen MD, Harmatz JS, Shader RI: Diazepam disposition determinants. Clin Pharmacol Ther 27:301–312, 1980. doi: 10.1038/clpt.1980.40)