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

The effect of a high‐protein meal on the hepatic clearance (Cl H ) of intravenous lidocaine, because of its conceptual importance in understanding first‐pass metabolic phenomena, was evaluated in nine healthy males. Our randomized crossover study demonstrated that mean Cl H rose from 1245 to 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 Cl H (r = 0.54; slope = ‐0.037% per ml/min; intercept = 67.2%; P < 0.15). In a separate study, it was observed that 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. These data suggest that the mean clearance of lidocaine is increased by stimulation of hepatic blood flow rate. Furthermore, the magnitude of this increase is consistent with expectations based on a simple physiologic model. Thus, these data provide experimental support for the hypothesis that 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. Clinical Pharmacology and Therapeutics (1981) 30, 455–460; doi: 10.1038/clpt.1981.188