Direct and cytokine-mediated effects of albumin-fused growth hormone, TV-1106, on CYP enzyme expression in human hepatocytes in vitro

Date
2018-04-16
Authors
Czerwinski, Maciej
Amunom, Immaculate
Piryatinsky, Victor
Hallak, Hussein
Sahly, Yousif
Bar-Ilan, Oren
Bolliger, Paul
Bassan, Merav
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley Subscription Services, Inc., A Wiley Company
Abstract
Some biologics can modulate cytokines that may lead to changes in expression of drugmetabolizing 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 (rhGH) or TV-1106, followed by isolation of the plasma and its application to human hepatocytes. While the treatment of blood with rhGH 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 rhGH then in the TV-1106-treated plasma (P < .05). While rhGH had little or no effect on CYP1A2 or CYP2C19 mRNA but increased CYP3A4 mRNA twofold, TV-1106 had little or no effect on cytochrome P450 (CYP) mRNAs in hepatocytes. Although the plasma from rhGH-treated blood lowered CYP1A2 activity, the TV-1106 plasma had no effect on CYP activities. The CYP1A2 activity was lower in the rhGH- 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 CYP1A2, CYP2C19 or CYP3A4-facilitated, direct or cytokine-driven DDI.
Description
Keywords
Carrier protein, CYP suppression, cytokine release, drug-drug interaction, growth hormone
Citation
Czerwi nski M, Amunom I, Piryatinsky V, et al. Direct and cytokine-mediated effects of albuminfused growth hormone, TV-1106, on CYP enzyme expression in human hepatocytes in vitro. Pharmacol Res Perspect. 2018; e00397.