Half-Life of Sulfonylureas in HNF1A and HNF4A Human MODY Patients is not Prolonged as Suggested by the Mouse Hnf1a(-/-) Model

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F15%3A43910322" target="_blank" >RIV/00216208:11120/15:43910322 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064173:_____/15:#0000491

Výsledek na webu

<a href="http://dx.doi.org/10.2174/1381612821666151008124036" target="_blank" >http://dx.doi.org/10.2174/1381612821666151008124036</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1381612821666151008124036" target="_blank" >10.2174/1381612821666151008124036</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Half-Life of Sulfonylureas in HNF1A and HNF4A Human MODY Patients is not Prolonged as Suggested by the Mouse Hnf1a(-/-) Model

Popis výsledku v původním jazyce

Sulfonylurea derivatives are widely used for clinical treatment of human subjects with Maturity Onset Diabetes of the Young (MODY) caused by mutations in HNF-1? or HNF-4? despite the mechanism leading to their hypersensitivity is incompletely understood.In Hnf1a-/- mice, serum concentrations and half-life of sulfonylurea derivatives are strongly increased. We thus hypothesized that reduced sulfonylurea derivatives clearance stands behind their therapeutic potential in human HNF1A/HNF4A MODY subjects. Design and Methods Single doses of 3 mg glipizide and 5 mg glibenclamide/glyburide were administered sequentially to seven HNF1A/HNF4A MODY subjects and six control individuals matched for their age, BMI and CYP2C9 genotype. Pharmacokinetic (plasma concentration levels, Cmax, tmax, t1/2, AUC) and pharmacodynamic parameters (glycemia, C-peptide and insulin plasma levels) were followed for 24 hours after drug administration. Results We provide the first evidence on the pharmacokinetics and

Název v anglickém jazyce

Half-Life of Sulfonylureas in HNF1A and HNF4A Human MODY Patients is not Prolonged as Suggested by the Mouse Hnf1a(-/-) Model

Popis výsledku anglicky

Sulfonylurea derivatives are widely used for clinical treatment of human subjects with Maturity Onset Diabetes of the Young (MODY) caused by mutations in HNF-1? or HNF-4? despite the mechanism leading to their hypersensitivity is incompletely understood.In Hnf1a-/- mice, serum concentrations and half-life of sulfonylurea derivatives are strongly increased. We thus hypothesized that reduced sulfonylurea derivatives clearance stands behind their therapeutic potential in human HNF1A/HNF4A MODY subjects. Design and Methods Single doses of 3 mg glipizide and 5 mg glibenclamide/glyburide were administered sequentially to seven HNF1A/HNF4A MODY subjects and six control individuals matched for their age, BMI and CYP2C9 genotype. Pharmacokinetic (plasma concentration levels, Cmax, tmax, t1/2, AUC) and pharmacodynamic parameters (glycemia, C-peptide and insulin plasma levels) were followed for 24 hours after drug administration. Results We provide the first evidence on the pharmacokinetics and

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Current Pharmaceutical Design

ISSN

1381-6128

e-ISSN

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Svazek periodika

21

Číslo periodika v rámci svazku

39

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

13

Strana od-do

5736-5748

Kód UT WoS článku

000365044900014

EID výsledku v databázi Scopus

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