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Rectal bioavailability of lidocaine in rats: absence of significant first-pass elimination.

Drugs administered rectally generally are considered to enter the systemic circulation without passing first through the liver since the lower hemorrhoidal veins do not drain into the portal system. To test this hypothesis, the systemic availability of the high clearance drug lidocaine was investigated in rats following oral (20 mg) and rectal (20 mg) administration to six rats and intraarterial (5 mg) administration to another six rats. Whole blood concentrations of lidocaine were determined by capillary GLC with nitrogen detection. Systemic availability was evaluated by two methods. For the rectal route, the results were 105.6 ± 43.3 and 83.1 ± 22.3% compared to those for intraarterial administration; for the oral route, these values were 7.7 ± 2.3 and 7.1 ± 2.3%. These results clearly indicate a significant bypass of the liver following rectal administration of lidocaine. Mean elimination half-lives following oral (54 ± 9 min) and rectal (79 ± 36 min) administration were not significantly different; however, rectal elimination half-lives sometimes were slightly prolonged. The mean peak concentration times of 11.5 ± 7.5 (oral) and 15.6 ± 10.6 (rectal) min were not significantly different whereas the mean peak concentrations were significantly different (p < 0.01) [0.92 ± 0.49 (oral) and 8.71 ± 3.30 (rectal) μg/ml]. The mean elimination half-life following intraarterial administration (33 ± 3 min) was significantly shorter than both the mean oral and rectal half-lives, and the calculated total blood clearance of lidocaine had an average value of 36 ± 9 ml/min. The results show that it is possible to bypass the liver, at least partially, when giving a high clearance drug rectally to rats. For lidocaine, this bypass is almost complete.