Clinical pharmacology. Clinical uses of pharmacokinetic principles in prescribing cardiac drugs

Knowledge of pharmacokinetics aids the clinician by providing dosing recommendations, and guidelines for alterations in dosing in the presence of abnormalities of cardiac, liver, and renal function. Drug disposition is the result of the processes of absorption, distribution, metabolism, and elimination. Absorption of orally administered drugs is dependent upon the physicochemical properties of the drug preparation, gastrointestinal function, and hepatic metabolism. A drug in the systemic circulation must be distributed to tissues in order to exert its effects. Distribution is usually rapid. This process may be altered by renal failure, changes in plasma protein binding, or other drugs. Changes in distribution characteristics may have a significant effect on drug blood levels. Many drugs are metabolized to compounds that have important clinical effects. In some cases, the metabolite may be more potent than the parent drug. In renal failure patients, the metabolite may accumulate and exert a greater effect than the parent drug. Elimination of a drug from the body quantitated as drug clearance. The rate of elimination also determines rate at which a drug accumulates in the body during chronic dosing. Pharmacokinetic calculations may be utilized to estimate the appropriate dosing regimen. This includes calculation of the loading dose, maintenance dose, and intravenous infusion rate. These estimates may be improved by measuring blood levels of the drug.