Open AccessDirect and cytokine‐mediated effects of albumin‐fused growth hormone, TV ‐1106, on CYP enzyme expression in human hepatocytes in vitro
Author(s) -
Czerwiński Maciej,
Amunom Immaculate,
Piryatinsky Victor,
Hallak Hussein,
Sahly Yousif,
BarIlan Oren,
Bolliger Paul,
Bassan Merav
Publication year - 2018
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.397
Subject(s) - albumin , cytokine , cytochrome p450 , medicine , pharmacology , endocrinology , in vitro , enzyme , hormone , chemistry , metabolism , biochemistry
Abstract Some biologics can modulate cytokines that may lead to changes in expression of drug‐metabolizing enzymes and cause drug‐drug interactions ( DDI ). DDI potential of TV ‐1106—an albumin‐fused growth hormone ( GH )—was investigated. In this study, human blood was exposed to recombinant human growth hormone (rh GH ) or TV ‐1106, followed by isolation of the plasma and its application to human hepatocytes. While the treatment of blood with rh GH increased multiple cytokines, treatment of blood with TV ‐1106 had no effect on any of the nine cytokines tested. The interleukin ( IL )‐6 concentration was higher in the rh GH then in the TV ‐1106‐treated plasma ( P < .05). While rh GH had little or no effect on CYP 1A2 or CYP 2C19 mRNA but increased CYP 3A4 mRNA twofold, TV ‐1106 had little or no effect on cytochrome P450 ( CYP ) mRNA s in hepatocytes. Although the plasma from rh GH ‐treated blood lowered CYP 1A2 activity, the TV ‐1106 plasma had no effect on CYP activities. The CYP 1A2 activity was lower in the rh GH ‐ then in the TV ‐1106‐plasma treated hepatocytes ( P < .05). The results indicated that fusing GH with albumin made TV ‐1106 an unlikely participant of CYP 1A2, CYP 2C19 or CYP 3A4‐facilitated, direct or cytokine‐driven DDI.