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LINCOLN, R.I.--(BUSINESS WIRE)--Nov. 30, 2005--MultiCell Technologies, Inc. (OTCBB: MCET - News) announced that AstraZeneca (NYSE:AZN - News) scientists presented a paper at the American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition concerning the use of the Company's Fa2N-4 immortalized human hepatocyte cells as an alternative model for drug induction studies.
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Because high quality normal human hepatocytes are expensive and difficult to obtain, immortalized human hepatocytes offer an attractive alternative for evaluating the induction of drug metabolism enzymes and transporters. AstraZeneca measured enzyme activities for CYP3A4 (formation of alpha-hydroxymidazolam), CYP2C9 (formation of 4'-hydroxydiclofenac), and CYP1A2 (formation of acetaminophen), and uptake of (3H) estradiol-17-(-glucuronide (E217G) and (3H) digoxin 72 hrs after treatment of test compounds. The results indicated low basal activity of CYP3A4 in Fa2N-4 cells, and a 5 to 10-fold increase in induction by rifampin (10 uM) across passages. AstraZeneca additionally reported that exposure of the Fa2N-4 cells to rifampin increased CYP2C9 activity by 2.1 fold, and exposure to naphthoflavone (25 uM) induced CYP1A2 activity by 7 and 11-fold in Fa2N-4 cells and normal human hepatocytes, respectively. In Fa2N-4 cells, treatment with AstraZeneca's proprietary drug lead candidates induced CYP1A2 activity by 2.5, 11 and 39-fold at a concentration of 1 uM, and by 7, 12 and 111-fold at a concentration of 10 uM depending upon the compound that was evaluated. In freshly obtained normal human hepatocytes, the same AstraZeneca proprietary compounds increased CYP1A2 activity by 1.0, 4.7, 27-fold at the concentration of 1 uM and 12, 1.1, 13-fold at the concentration of 10 uM depending upon the compound that was evaluated. AstraZeneca found no significant temperature-dependent uptake of E217G in Fa2N-4 cells. In contrast, AstraZeneca observed that digoxin uptake at 2 min was 5.6 and 1.3 (pmol/mg protein) at 37-degrees C and 4-degrees C, respectively while rifampin had no significant effect on uptake of E217G and digoxin. AstraZeneca's scientists concluded that MultiCell's Fa2N-4 cells responded to CYP450 inducers in a manner similar to freshly obtained normal human hepatocytes. AstraZeneca's scientists stated that further studies will be conducted to determine if drug transporters can be induced in MultiCell's Fa2N-4 immortalized human hepatocytes. Six AstraZeneca scientists authored the research paper presented at the recent AAPS meeting.
Dr. Ron Faris, Sr. Vice President and CSO, noted, "We are gratified that an additional validation of the Fa2N-4 cell's utility was presented at this respected forum by one of the top 6 pharmaceutical companies in the world." |
