First‐pass elimination of lidocaine in the rabbit after peroral and rectal route of administration

Abstract

Lidocaine shows pronounced first-pass metabolism upon peroral administration in man (about 30 per cent peroral bioavailability). Since the rectal bioavailability is about 65 per cent in man it is assumed that some drug is directly absorbed into systemic circulation by-passing the liver. In rats peroral bioavailability is about 8 per cent whereas rectal bioavailability is about 100 per cent. This indicates that the rat is not a suitable model to study rectal lidocaine dosage forms. The purpose of this study was to investigate lidocaine disposition and bioavailability in rabbits after peroral and rectal administration. The peroral bioavailability in rabbits was found to be about 6 per cent and the rectal bioavailability is about 33 per cent. The results indicate that the rabbit is a suitable model for the study of systemic absorption of rectal lidocaine dosage forms.

Avoidance of hepatic first-pass effect in the rabbit via rectal route of administration

“…enters whole body blood directly, bypassing the portal circulation. Ritschel et al [5] estimated an f nh of 29.7% (range 5 -50%) from respective EBA (oral 6%, rectal 34%), assuming complete absorption via oral and rectal routes. In our experiments, the EBA (average of 60%) as well as f nh of rectal administration was considerably higher.…”

“…The rabbit has been frequently used as an experimental system in the development of preparations for rectal administration and studies of drug metabolism [1]. Ritschel et al [5] reported that avoidance of hepatic first-pass effect was about 30% assuming complete absorption of lidocaine by oral and rectal routes. Gastric contents and type of preparation, however, are likely to affect absorption [6,7], and the above assumptions may not be accurate.…”