Development of drug metabolism simulator using PUF/hepatocyte spheroid culture. - Study of acetaminophen metabolism by hybrid artificial liver system

K. Nakazawa, H. Mizumoto, H. Ijima, T. Matsushita, K. Funatsu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Primary rat hepatocytes in monolayer and spheroid stationary culture converted acetaminophen to conjugated acetaminophen with glucuronide and sulfate. The metabolic activity of hepatocytes/spheroid stationary culture system was about 2 times higher than that of monolayer culture and was maintained for 10 days. We developed a device of liver model using a PUF/spheroid packed-bed module. The acetaminophen metabolic activity of hepatocytes/spheroid perfused culture system was about 2 times higher than that of stationary culture. Acetaminophen clearance and extraction ratio of hepatocytes/spheroid in the device were 0.013 ± 0.001ml/min/module and 0.0093 ± 0.0018/108 cells(g-liver), respectively. The value of extraction ratio was comparable with in vivo value, 0.016 ± 0.005/108 cells reported by S. D. Studenberg using rat whole liver perfusion technique. Consequently, PUF/spheroid culture seems to provide a promising culture system as a drag metabolism simulator which will be used for drug screening in vivo.

Original languageEnglish
Pages (from-to)713-718
Number of pages6
JournalJapanese Journal of Artificial Organs
Volume26
Issue number3
Publication statusPublished - Jan 1 1997

All Science Journal Classification (ASJC) codes

  • Biophysics

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