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- W2152912184 abstract "To assess avoidance of hepatic first-pass effect of drugs, we undertook in situ experiments using rectal administration of lidocaine in the rabbit. We also employed in situ duodenal route to estimate first-pass metabolism across the gastrointestinal mucosa. Rabbits were administered lidocaine HCl intravenously (i.v., 50 mg/20 min) and portally (i.p.v., 33.3, 16.7, 8.3 mg/20 min) and avoidance of hepatic first-pass effect (Fh) was calculated from the area under curve (AUC). Fh was about 30% and did not vary with increasing i.p.v. dose. Intravenous and i.p.v. administration was followed by duodenal (i.d.) or rectal (i.r.) administration and the absorption (fa), Fh, and avoidance of first-pass effect in the duodenal mucosal membrane (Fm) were determined. With i.d. administration, lidocaine was absorbed completely with negligible first-pass effect in the mucosa (Fm=1). On the other hand, while lidocaine was also absorbed almost completely via the i.r. route, avoidance of first-pass effect was 60%, representing twice the bioavailability via i.d. administration. On the basis of these data, assuming that the first-pass effect in the rectal mucosa was negligible, we estimate the fraction of rectal venous drainage bypassing the portal circulation and thus hepatic metabolism (fnh) to be about 40%." @default.
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- W2152912184 date "1998-12-01" @default.
- W2152912184 modified "2023-09-26" @default.
- W2152912184 title "Avoidance of hepatic first-pass effect in the rabbit via rectal route of administration" @default.
- W2152912184 doi "https://doi.org/10.1002/(sici)1099-081x(199812)19:9<589::aid-bdd141>3.0.co;2-2" @default.
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