Drug Pharmacokinetics in Cardiac and Hepatic Disease

The rational administration of a drug to a patient requires knowledge of the anticipated efficacy and toxicity of the drug dose that is administered. When knowledge of how a given patient will absorb and eliminate a drug is coupled with knowledge of the pharmacologic effect of a given amount of the drug, a drug dose can be selected that will result in clinical efficacy with minimal toxicity. After a dosing regimen is instituted, direct clinic.!l obser­ vations for efficacy and toxicity and laboratory measurements of drug con­ centrations in plasma or blood may then be used to modify the initial regimen (1). These observations are especially important when drugs with low therapeutic indices are used. To assist the physician in the development of a rational dosing regimen, the science of pharmacokinetics provides information about the time course of the amount of drug in the body in the expectation that this information will correlate, directly or indirectly, with the time course of drug efficacy and toxicity. Investigations of drug absorption into the body, distribution within, and elimination from the body (the latter two processes defined as drug disposition) have been performed frequently in healthy subjects on the assumption that kinetic parameters defi ned in a small number of healthy individuals would apply to various patient populations (2). Although this assumption forms the basis for many pharmacokinetic investigations that are performed to evaluate drugs for clinical use, several clinical investiga­ tions have now documented that drug absorption and disposition parame­ ters in healthy individuals may differ widely from those observed in patients