Acetaminophen presystemic biotransformation vs bioavailability in therapeutical dosage range

Abstract

The influence of dose on the absorption and presystemic biotransformation of acetaminophen was studied in 15 healthy volunteers after administration of 3 different oral doses (250 mg, 500 mg, 750 mg) following a 3 x 3 Latin Square Design. The analytical method developed (High Performance Liquid Chromatography, HPLC) allows the rapid and simultaneous determination of acetaminophen and its major metabolites (its glucuronide and sulphate conjugates) by direct injection of urine samples. The statistical analysis did not reveal significant differences (alpha < 0.05) among treatments in the percentage of dose excreted and MRT and VRT values. Consequently, our results indicate that the absorption and biotransformation of acetaminophen is not affected by the dose in the usual therapeutical range.

Importance of entero‐salivary recirculation in paracetamol pharmacokinetics

“…After oral administration, a fraction of the dose is absorbed from the GI reaching the systemic circulation. The principal metabolites formed in the liver are the conjugates of paracetamol with glucuronic and sulfuric acids eliminated by biliary and renal excretions [11,17,18]. The conjugates are stored in the gallbladder until some stimulus evokes its liberation.…”