Bioequivalence study of two formulations of itraconazole 100 mg capsules in healthy volunteers under fed conditions: a randomized, three-period, reference-replicated, crossover study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50014831" target="_blank" >RIV/62690094:18470/18:50014831 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1080/17425255.2018.1503649" target="_blank" >http://dx.doi.org/10.1080/17425255.2018.1503649</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/17425255.2018.1503649" target="_blank" >10.1080/17425255.2018.1503649</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Bioequivalence study of two formulations of itraconazole 100 mg capsules in healthy volunteers under fed conditions: a randomized, three-period, reference-replicated, crossover study

Popis výsledku v původním jazyce

Background: The aim of the study was to evaluate the bioequivalence of two itraconazole 100 mg capsule formulations. Research design and methods: The single-center, open-label, randomized, three-period, three-sequence, reference-replicated, cross-over study included 38 healthy subjects under fed conditions. In each study period (separated by a 14-day washout), a single oral dose of the test (T) or reference (R) product was administered. Blood samples were collected at pre-dose and up to 72.0 h after administration. The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxy itraconazole, were AUC(0-72h), AUC(0-proportional to), C-max, T-max, T-1/2 and K-el. Results: The 90% CI for the test/reference geometric means ratio for the parent compound, itraconazole, was in the range from 85.29% to 116.07% for AUC(0-72h.) Since the coefficient of variation (CV) for the reference product was 44.95% for C-max, the 90% CI for this parameter for itraconazole was 93.49-133.78%, which was within the proposed limits of the EMA for bioequivalence of 72.15-138.59%. During the study, 4 subjects encountered a total of 14 mild adverse events. Conclusions: The use of the reference-scaling approach with 3-period design (TRR, RTR, and RRT) was an efficient way to demonstrate that two commercially available oral itraconazole formulations met the predetermined bioequivalence criteria.

Název v anglickém jazyce

Bioequivalence study of two formulations of itraconazole 100 mg capsules in healthy volunteers under fed conditions: a randomized, three-period, reference-replicated, crossover study

Popis výsledku anglicky

Background: The aim of the study was to evaluate the bioequivalence of two itraconazole 100 mg capsule formulations. Research design and methods: The single-center, open-label, randomized, three-period, three-sequence, reference-replicated, cross-over study included 38 healthy subjects under fed conditions. In each study period (separated by a 14-day washout), a single oral dose of the test (T) or reference (R) product was administered. Blood samples were collected at pre-dose and up to 72.0 h after administration. The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxy itraconazole, were AUC(0-72h), AUC(0-proportional to), C-max, T-max, T-1/2 and K-el. Results: The 90% CI for the test/reference geometric means ratio for the parent compound, itraconazole, was in the range from 85.29% to 116.07% for AUC(0-72h.) Since the coefficient of variation (CV) for the reference product was 44.95% for C-max, the 90% CI for this parameter for itraconazole was 93.49-133.78%, which was within the proposed limits of the EMA for bioequivalence of 72.15-138.59%. During the study, 4 subjects encountered a total of 14 mild adverse events. Conclusions: The use of the reference-scaling approach with 3-period design (TRR, RTR, and RRT) was an efficient way to demonstrate that two commercially available oral itraconazole formulations met the predetermined bioequivalence criteria.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

EXPERT OPINION ON DRUG METABOLISM &amp; TOXICOLOGY

ISSN

1742-5255

e-ISSN

—

Svazek periodika

14

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

979-988

Kód UT WoS článku

000444089500011

EID výsledku v databázi Scopus

2-s2.0-85052146917