期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 101, 期 10, 页码 3989-4002出版社
WILEY-BLACKWELL
DOI: 10.1002/jps.23262
关键词
hepatic clearance; hepatic metabolism; hepatocytes; metabolic clearance; CYP enzymes; cytochrome P450; clearance; flavin monooxygenases (FMO)
Primary human hepatocytes are widely used for metabolic stability evaluations. However, there are limited data directly comparing phase I and phase II drug-metabolizing enzymes in fresh and cryopreserved hepatocytes prepared from the same human donor liver. We evaluated the metabolic competency of human hepatocytes prepared from seven donor tissues before and after cryopreservation. Temporal-dependent enzyme activity in suspension and matched adherent cultures of primary human hepatocytes was also assessed. Cryopreservation of hepatocytes resulted in statistically significant increases in activities of CYP1A2, CYP2B6, CYP2C9, CYP2D6, and CYP3A but not CYP2C8, CYP2C19, FMO, UGT, and SULT, relative to fresh hepatocytes. In suspension cultures of hepatocytes, enzyme stabilities were as follows: UGT
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