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

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.