CLEARANCE AND BIOLOGIC HALF-LIFE AS INDICES OF INTRINSIC HEPATIC METABOLISM

¹ Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo, New York and College of Pharmacy, University of Kentucky, Lexington, Kentucky

Clearance and half-life are evaluated as indices of the intrinsic capacity of the liver to metabolize drugs. The utility of these parameters as indices of hepatic elimination is highly dependent upon the pharmacokinetic characteristics of a particular drug. For drugs which confer the pharmacokinetic characteristics of a single compartment model on the body, both half-life and clearance serve as meaningful measures of hepatic elimination. However, for a drug which confers multicompartment characteristics on the body, biologic half-life does not reflect properly the intrinsic metabolic activity of the liver. Clearance, on the other hand, is a direct measure of this activity regardless of the number of compartments conferred upon the body by a drug provided the liver is an integral part of the central compartment. For drugs subject to first-pass metabolism, the applicability of clearance as an index of hepatic metabolism is considerably more limited. After the intravenous administration of a drug, which is subject to first-pass metabolism on oral administration, the reliability of body clearance as an index of hepatic elimination becomes less meaningful as the potential for first-pass metabolism increases. After oral administration, however, body clearance appears to reflect directly intrinsic metabolic activity regardless of the extent of first-pass metabolism.

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