Please use this identifier to cite or link to this item: https://doi.org/10.1023/A:1020901328583
Title: Evidence for dissolution rate-limited absorption of COL-3, a matrix metalloproteinase inhibitor, leading to the irregular absorption profile in rats after oral administration
Authors: Li, J.
Huynh, H.
Chan, E. 
Keywords: COL-3
Dissolution rate-limited absorption
Double- or plateau-peak phenomenon
Flip-flop situation
Irregular absorption
Matrix metalloproteinase inhibitor
Issue Date: 1-Nov-2002
Citation: Li, J., Huynh, H., Chan, E. (2002-11-01). Evidence for dissolution rate-limited absorption of COL-3, a matrix metalloproteinase inhibitor, leading to the irregular absorption profile in rats after oral administration. Pharmaceutical Research 19 (11) : 1655-1662. ScholarBank@NUS Repository. https://doi.org/10.1023/A:1020901328583
Abstract: Purpose. This study was undertaken to elucidate the underlying mechanism of the irregular absorption profiles of COL-3, a matrix metalloproteinase inhibitor, with a double- or plateau-peak concentration after a single oral dose administration of COL-3 suspension to rats. Methods. The gastrointestinal absorption profiles of COL-3 in rats were assessed by comparing serum drug concentration curves after the following various modes of drug administration: oral and intraduodenal doses, oral doses of COL-3 in fine and coarse suspensions, intraduodenal dosing to the bile-duct intact and cannulated (BDC) rats, and oral doses with and without food. In addition, the biliary excretion of COL-3 in the BDC rats was examined. Results. Neither variable gastric emptying nor enterohepatic recycling was the source of the irregular gastrointestinal absorption of COL-3 in rats. Reduction in particle size, presence of food and endogenous bile emerged as the determinants of the oral absorption of COL-3 by enhancing the dissolution of the solid drug in the gastrointestinal fluids. Flip-flop of the absorption and elimination rate constants was noted only for COL-3 after intraduodenal administration of the coarse suspension to the BDC rats with the bile flow diverged out of the body. Conclusions. Variability in dissolution rate-limited absorption was the main cause of the irregular absorption of COL-3 after oral administration of its solid dosage form.
Source Title: Pharmaceutical Research
URI: http://scholarbank.nus.edu.sg/handle/10635/105939
ISSN: 07248741
DOI: 10.1023/A:1020901328583
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