A Novel In vitro Experimental System for the Evaluation of Enteric Drug Metabolism: Cofactor-Supplemented Permeabilized Cryopreserved Human Enterocytes (MetMax™ Cryopreserved Human Enterocytes)

Title:A Novel In vitro Experimental System for the Evaluation of Enteric Drug Metabolism: Cofactor-Supplemented Permeabilized Cryopreserved Human Enterocytes (MetMax™ Cryopreserved Human Enterocytes)

Volume: 12 Issue: 2

Author(s): Albert P. Li*, Kirsten Amaral and Ming-Chih D. Ho

Affiliation:

• In vitro ADMET Laboratories Inc., 9221 Rumsey Road, Suite 8, Malden, MA 02148, USA and Boston Hepatocyte Technology Center, In vitro ADMET Laboratories, 389 Main St, Ste 301, Malden, MA 02148,United States

Keywords: Permeabilized, cryopreserved human enterocytes, MMHE, CCHE, Drug metabolism enzyme (DME), enteric drug metabolism.

Abstract: Background: We report here an evaluation of a novel experimental system- cofactorsupplemented permeabilized cryopreserved human enterocytes (MetMax™ cryopreserved human enterocytes (MMHE), patent pending) for applications in the evaluation of enteric drug metabolism. A major advantage of MMHE over Conventional Cryopreserved Human Enterocytes (CCHE) is the simplification of the use procedures including storage at -80°C instead of in liquid nitrogen, and use of the cells immediately after thawing without a need for centrifugation and microscopic evaluation of cell density and viability and cell density adjustment.

Methods: In this study, we compared MMHE and CCHE in key phase 1 oxidation and phase 2 conjugation Drug Metabolism Enzyme (DME) activities that we recently reported for cryopreserved human enterocytes: CYP2C9 (diclofenac 4’- hydroxylation), CYP2C19 (s-mephenytoin hydroxylation), CYP3A4 (midazolam 1’-hydroxylation), CYP2J2 (astemizole O-demethylation), uridine 5'-diphosphoglucuronosyltransferase (UGT; 7-hydroxycoumarin glucuronidation), sulfotransferase (SULT; 7- hydroxycoumarin sulfation), N-acetyl transferase-1 (NAT-1; p-benzoic acid N-acetylation), and carboxyesterase- 2 (CES-2; hydrolysis of irinotecan to SN38). Both CCHE and MMHE were active in all the DME pathways evaluated, with specific activities of MMHE ranged from 142% (CYP2C9) to 1713% (UGT) of that for CCHE. β-hydroxylation and testosterone 6.

Result and Conclusion: Our results suggest that the MMHE system represents a convenient and robust in vitro experimental system for the evaluation of enteric drug metabolism.

Cite this article as:

Li P. Albert *, Amaral Kirsten and Ho D. Ming-Chih , A Novel In vitro Experimental System for the Evaluation of Enteric Drug Metabolism: Cofactor-Supplemented Permeabilized Cryopreserved Human Enterocytes (MetMax™ Cryopreserved Human Enterocytes), Drug Metabolism Letters 2018; 12 (2) . https://dx.doi.org/10.2174/1872312812666180820142141