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Calcitonin gene‐related peptide and somatostatin releases correlated with the area under the lafutidine concentration–time curve in human plasma
Author(s) -
Ikawa K.,
Shimatani T.,
Azuma Y.,
Inoue M.,
Morikawa N.
Publication year - 2006
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.2006.00749.x
Subject(s) - somatostatin , calcitonin gene related peptide , chemistry , calcitonin , gastrin , endocrinology , medicine , pharmacokinetics , peptide hormone , neuropeptide , blood plasma , radioimmunoassay , area under the curve , receptor , secretion
Summary Objective: To examine the effects of the histamine H 2 ‐receptor antagonist, lafutidine, at clinical dosage (10 mg tablet after a standardized meal) on plasma levels of the gastrointestinal peptides, calcitonin gene‐related peptide (CGRP), somatostatin and gastrin. Methods: Six healthy male volunteers ate a standardized meal, and received either lafutidine orally at a dose of 10 mg or water only (control). Blood samples were taken before and up to 4 h after the drug administration. Plasma lafutidine concentrations were determined by high pressure liquid chromatography. Pharmacokinetic analysis of lafutidine was performed using one‐compartmental model. The levels of immunoreactive substances of plasma CGRP, somatostatin and gastrin were measured by enzyme immunoassay, and the amount of peptide release was calculated by the trapezoidal method. Results: Lafutidine significantly increased plasma CGRP levels at 1, 1·5, 2·5 and 4 h and the total amount of CGRP release (192 ± 14·0 pg·h/mL) compared with the control group (128 ± 21·5 pg·h/mL). Lafutidine significantly increased the plasma somatostatin levels at 1 and 1·5 h, and the total amount of somatostatin released (107 ± 18·2 pg·h/mL) compared with the control (78·4 ± 7·70 pg·h/mL). The area under the drug concentration–time curve ( AUC ) from 0 to 4 h after administration correlated well with the Δ‐CGRP and Δ‐somatostatin release but not with total amount of gastrin released. However, plasma gastrin levels were significantly elevated at 1·5 h after drug administration. Conclusion: Lafutidine at clinical dosage increases plasma CGRP and the somatostatin. The amounts released correlated with the AUC of lafutidine in humans. These results suggest that the increased release of CGRP and somatostatin may contribute to its gastroprotective and anti‐acid secretory effect.