Calcitonin gene-related peptide and somatostatin releases correlated with the area under the lafutidine concentration–time curve in human plasma
- 1 August 2006
- journal article
- research article
- Published by Hindawi Limited in Journal of Clinical Pharmacy & Therapeutics
- Vol. 31 (4), 351-356
- https://doi.org/10.1111/j.1365-2710.2006.00749.x
Abstract
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.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. 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 Delta-CGRP and Delta-somatostatin release but not with total amount of gastrin released. However, plasma gastrin levels were significantly elevated at 1.5 h after drug administration.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.Keywords
This publication has 17 references indexed in Scilit:
- Development of A Pharmacokinetic Analysis Program Based on Nonlinear Least Squares Method Available in Microsoft Windows XP (MULTI-Win)Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences), 2004
- Sensitizing effects of lafutidine on CGRP‐containing afferent nerves in the rat stomachBritish Journal of Pharmacology, 2002
- Enzyme Immunoassay of Calcitonin Gene-Related Peptide-like Immunoreactive Substance in Human Plasma and Saliva.Japanese Journal of Hospital Pharmacy, 1998
- Stimulation of mucin biosynthesis in rat gastric mucosa by FRG-8813 and its structural analogsEuropean Journal of Pharmacology, 1996
- Gastroprotective Activity of FRG-8813, a Novel Histamine H2-Receptor Antagonist, in RatsThe Japanese Journal of Pharmacology, 1995
- Enzyme Immunoassay of Gastrin in Human Plasma.CHEMICAL & PHARMACEUTICAL BULLETIN, 1993
- Enzyme immunoassay of somatostatin(SS)-like immunoreactive substance in bovine milk.CHEMICAL & PHARMACEUTICAL BULLETIN, 1990
- Calcitonin gene-related peptides relax guinea pig and rat gastric smooth muscleEuropean Journal of Pharmacology, 1989
- Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processingNature, 1983
- A pharmacokinetic analysis program (multi) for microcomputer.Journal of Pharmacobio-Dynamics, 1981