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Age‐dependent changes in first‐pass metabolism of acetaminophen in rats
Author(s) -
Hirate Junji,
Zhu Chunyan,
Horikoshi Isamu,
Bhargava Vijay O.
Publication year - 1991
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510120205
Subject(s) - acetaminophen , pharmacokinetics , metabolism , oral administration , medicine , first pass effect , drug metabolism , drug , pharmacology , glucuronide , anesthesia
The contribution of gastrointestinal tract (GIT), liver, and lung towards the first‐pass metabolism of acetaminophen was examined using 3‐week‐old, 10‐week‐old and 1‐year‐old rats after administration of 30mgkg −1 doses by intra‐arterial, intravenous, intraperitoneal, and oral routes. Plasma concentrations of acetaminophen and its two major metabolities, acetaminophen glucuronide and acetaminophen sulfate, were measured for about 5h after drug administration. Total oral extraction of acetaminophen was extensive in 10‐week‐old and 1‐year‐old rats ( E o = 0·46) and the major contribution to the overall first‐pass metabolism was due to the GIT ( E g = 0·50–0·53). Oral extraction in 3‐week‐old rats was minimal ( E o = 0·10) and there did not appear to be an extraction by the GIT ( E g = 0·00). These results suggest that the ability of GIT to metabolize acetaminophen to glucuronide and sulfate is undeveloped in the infant rats. No changes in the contribution of different organs to the first‐pass metabolism of acetaminophen was observed 10 weeks after birth. Pharmacokinetic parameters for acetaminophen in infant rats (3‐week‐old) and 10‐week‐old rats were similar after drug administration by the intra‐arterial and intravenous routes.