Rectal bioavailability of lidocaine in the dog: evaluation of first-pass elimination

The disposition of lidocaine was studied in beagle dogs after I.V., P.O. and rectal administration. Lidocaine HCl solution was used for the I.V. and P.O. studies. For rectal administration 3 gels were prepared: 1) lidocaine base in a hydrophilic vehicle, 2) lidocaine HCl in a hydrophilic vehicle, and 3) lidocaine base in a lipophilic vehicle. The gels were administered 3 cm deep in the rectum. Additionally, the gel of lidocaine HCl in a hydrophilic vehicle was also administered 10 cm deep in the rectum. No significant differences between I.V. and all extravascular administrations were observed for terminal half-life, total clearance and apparent volume of distribution. The systemic bioavailability after P.O. was 31%, and between 32% and 53% for the rectal dosage forms. The lidocaine base in lipophilic vehicle had the lowest systemic availability, the lowest peak concentration and the longest time to peak, whereas the lidocaine HCl in a hydrophilic vehicle, inserted 10 cm deep into the rectum, had the highest systemic bioavailability, highest peak concentration and shortest time to peak. The dog seems to be an excellent model for evaluation of peroral and rectal first-pass elimination.