|
KMID : 0369820060360040263
|
|
Jorunal of Korean Pharmaceutical Sciences
2006 Volume.36 No. 4 p.263 ~ p.269
|
|
|
The Design and Fabrication of μCCA-μGI Device for Toxicity Evaluation of Acetaminophen
|
|
장정윤/Chang JY
Michael L. Shuler
|
|
|
Abstract
|
|
|
|
Deficiencies in the early ADMET(absorption, distribution, metabolism, elimination and toxicity) information on drug candidate extract a significant economic penalty on pharmaceutical firms. Microscale cell culture analogue-microscale gastrointestinal(μCCA?μGI) device using Caco 2, L2 and HEp G2/C3A cells, which mimic metabolic process after absorption occurring in humans was used to investigate the toxicity of the model chemical, acetaminophen(AAP). The toxicity of acetaminophen determined after induction of CYP 1A1/2 in Caco 2 cells was not significant. In a coculture system, although no significant reduction in viability of HEp G2/C3A and L2 cells was found, approximately 5 fold increase in the CYP 1A1/2 activity was observed. These results appear to be related to organ-organ interaction. The oral administration of a drug requires addition of the absorption process through small intestine to the current μCCA device. Therefore, a perfusion coculture system was employed for the evaluation of the absolution across the small intestine and resulting toxicity in the liver and lung. This system give comprehensive and physiologic information on oral uptake and resulting toxicity as in the body. The current μCCA device can be used to demonstrate the toxic effect due to organ to organ interaction after oral administration.
|
|
|
KEYWORD
|
|
|
μCCA(Cell culture analogue), Acetaminophen, CYP 1A1/2
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|