Liu Z.,Central South University |
Zhang B.,Central South University |
Guo X.,Central South University |
Chen L.,Central South University |
And 3 more authors.
International Journal of Clinical Pharmacology and Therapeutics | Year: 2014
Objectives: This study was designed to determine whether xanthine oxidoreductase (XOR) is involved in Isosorbide- 5-mononitrate (IS-5-MN) metabolism, and to elucidate the role of the neuropeptide calcitonin gene-related peptide (CGRP) in the IS-5-MN response. Methods: In 15 Chinese volunteers, we observed the relationship between baseline XOR-mRNA expression in peripheral blood mononuclear cells (PBMCs) and the response to 20 mg IS-5-MN. IS-5- MN pharmacokinetics profiles, changes in plasma concentrations of CGRP, and CGRPmRNA expression in PBMCs were assessed in vivo and in vitro. Results: Individuals with a lower baseline XOR-mRNA expression showed lower plasma XOR activity and significantly greater changes in SBP (ΔSBP) after IS-5-MN administration. Individuals with a lower baseline XOR-mRNA expression also showed significantly greater increases in plasma concentrations of CGRP. There were no differences in IS-5-MN AUC between the two groups. IS-5-MN significantly up-regulated the expression of CGRP α- and CGRP β-mRNA in PBMCs, which were not affected by the XOR inhibitor allopurinol. Conclusions: Our study suggests that CGRP may contribute to the response to IS-5 MN in a XOR-independent pathway. ©2015 Dustri-Verlag Dr. K. Feistle.