Effect of food on lidocaine kinetics: Mechanism of food-related alteration in high intrinsic clearance drug elimination

Publisher Website
Google Scholar
Abstract
The effect of a high-protein meal on the hepatic clearance (ClH) of i.v. lidocaine, because of its conceptual importance in understanding 1st-pass metabolic phenomena, was evaluated in 9 healthy males. A randomized crossover study demonstrated that mean ClH rose from 1245-1477 ml/min (P < 0.03) as a result of the meal (i.e., mean area under the blood concentration-time curve decreased 20%). The magnitude of the change in clearance correlated weakly with fasting ClH (r = 0.54; slope = -0.037% per ml/min; intercept = 67.2%; P < 0.15). In a separate study the meal did not influence lidocaine serum protein binding; the free fraction of lidocaine in samples drawn from the subjects in the fasting state averaged 0.305 .+-. 0.027, while that from subjects who had eaten was 0.321 .+-. 0.042. The mean clearance of lidocaine is increased by stimulation of hepatic blood flow rate. The magnitude of this increase is consistent with expectations based on a simple physiologic model. Transient increases in splanchnic blood flow rate observed after a high-protein meal may explain apparent improvement of the oral bioavailability of model high intrinsic clearance drugs.

This publication has 6 references indexed in Scilit: