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Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: The effect of water and timing of meal intake on oral delivery of Salmon Calcitonin
BACKGROUND: To investigate the influence of water intake and dose timing on the pharmacokinetic and pharmacodynamic parameters of an oral formulation of salmon calcitonin (sCT). METHODS: The study was a randomized, partially-blind, placebo-controlled, single dose, exploratory crossover phase I study...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551583/ https://www.ncbi.nlm.nih.gov/pubmed/18782439 http://dx.doi.org/10.1186/1472-6904-8-5 |
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author | Karsdal, Morten A Byrjalsen, Inger Riis, Bente J Christiansen, Claus |
author_facet | Karsdal, Morten A Byrjalsen, Inger Riis, Bente J Christiansen, Claus |
author_sort | Karsdal, Morten A |
collection | PubMed |
description | BACKGROUND: To investigate the influence of water intake and dose timing on the pharmacokinetic and pharmacodynamic parameters of an oral formulation of salmon calcitonin (sCT). METHODS: The study was a randomized, partially-blind, placebo-controlled, single dose, exploratory crossover phase I study. 56 healthy postmenopausal women were randomly assigned to receive five treatments. The treatments comprised a combination of study medication (SMC021 (0.8 mg sCT + 200 mg 5-CNAC), SMC021 placebo, or 200 IU Miacalcic(® )NS nasal spray), water volume given with the tablet (50 or 200 ml water), and time between dosing and meal (10, 30, or 60 minutes pre-meal). Plasma sCT levels and changes in the bone resorption (C-terminal telopeptide of collagen type I) was investigated. Trial regristration RESULTS: Oral delivery of 0.8 mg of sCT with 50 ml of water compared to that with 200 ml water resulted in a two-fold increase in maximum concentration (C(max )and AUC(0–4)) of plasma sCT but comparable time to reach maximum concentration (T(max)). The sCT AUC(0–4 )with 50 ml of water was 4-fold higher than that obtained with nasal calcitonin. The increased absorption of sCT resulted in increased efficacy demonstrated by AUC of the relative change of serum CTX-I measured in the 6 hours post dosing. CONCLUSION: 0.8 mg sCT with 50 ml of water taken 30 and 60 minutes prior to meal time resulted in optimal pharmacodynamic and pharmacokinetic parameters. The data suggest that this novel oral formulation may have improved absorption and reduction of bone resorption compared to that of the nasal form. |
format | Text |
id | pubmed-2551583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-25515832008-09-24 Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: The effect of water and timing of meal intake on oral delivery of Salmon Calcitonin Karsdal, Morten A Byrjalsen, Inger Riis, Bente J Christiansen, Claus BMC Clin Pharmacol Research Article BACKGROUND: To investigate the influence of water intake and dose timing on the pharmacokinetic and pharmacodynamic parameters of an oral formulation of salmon calcitonin (sCT). METHODS: The study was a randomized, partially-blind, placebo-controlled, single dose, exploratory crossover phase I study. 56 healthy postmenopausal women were randomly assigned to receive five treatments. The treatments comprised a combination of study medication (SMC021 (0.8 mg sCT + 200 mg 5-CNAC), SMC021 placebo, or 200 IU Miacalcic(® )NS nasal spray), water volume given with the tablet (50 or 200 ml water), and time between dosing and meal (10, 30, or 60 minutes pre-meal). Plasma sCT levels and changes in the bone resorption (C-terminal telopeptide of collagen type I) was investigated. Trial regristration RESULTS: Oral delivery of 0.8 mg of sCT with 50 ml of water compared to that with 200 ml water resulted in a two-fold increase in maximum concentration (C(max )and AUC(0–4)) of plasma sCT but comparable time to reach maximum concentration (T(max)). The sCT AUC(0–4 )with 50 ml of water was 4-fold higher than that obtained with nasal calcitonin. The increased absorption of sCT resulted in increased efficacy demonstrated by AUC of the relative change of serum CTX-I measured in the 6 hours post dosing. CONCLUSION: 0.8 mg sCT with 50 ml of water taken 30 and 60 minutes prior to meal time resulted in optimal pharmacodynamic and pharmacokinetic parameters. The data suggest that this novel oral formulation may have improved absorption and reduction of bone resorption compared to that of the nasal form. BioMed Central 2008-09-09 /pmc/articles/PMC2551583/ /pubmed/18782439 http://dx.doi.org/10.1186/1472-6904-8-5 Text en Copyright © 2008 Karsdal et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Karsdal, Morten A Byrjalsen, Inger Riis, Bente J Christiansen, Claus Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: The effect of water and timing of meal intake on oral delivery of Salmon Calcitonin |
title | Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: The effect of water and timing of meal intake on oral delivery of Salmon Calcitonin |
title_full | Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: The effect of water and timing of meal intake on oral delivery of Salmon Calcitonin |
title_fullStr | Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: The effect of water and timing of meal intake on oral delivery of Salmon Calcitonin |
title_full_unstemmed | Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: The effect of water and timing of meal intake on oral delivery of Salmon Calcitonin |
title_short | Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: The effect of water and timing of meal intake on oral delivery of Salmon Calcitonin |
title_sort | optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: the effect of water and timing of meal intake on oral delivery of salmon calcitonin |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551583/ https://www.ncbi.nlm.nih.gov/pubmed/18782439 http://dx.doi.org/10.1186/1472-6904-8-5 |
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