Pharmacokinetic Variability in Pre-Clinical Studies: Sample Study with Abiraterone in Rats and Implications for Short-Term Comparative Pharmacokinetic Study Designs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F22%3A10443335" target="_blank" >RIV/00064165:_____/22:10443335 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/22:10443335 RIV/00216208:11310/22:10443335

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=55BuMqBvX3" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=55BuMqBvX3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/pharmaceutics14030643" target="_blank" >10.3390/pharmaceutics14030643</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pharmacokinetic Variability in Pre-Clinical Studies: Sample Study with Abiraterone in Rats and Implications for Short-Term Comparative Pharmacokinetic Study Designs

Popis výsledku v původním jazyce

One of the major concerns for all in vivo experiments is intra- and inter-subject variability, which can be a great source of inaccuracy. The aim of this study is, therefore, to estimate the ability of parallel vs. cross-over design studies in order to describe the relative pharmacokinetic performance of the studied drug formulations. We analyzed the data from a drug development program that examined the performance of innovative abiraterone acetate formulations against the identical reference product in three stages. In stages 1-3, groups A-F were dosed with the reference product once in a parallel manner. Stage 4 was performed to evaluate the intra-individual variability (IIV) by repeated administration of the reference product to the same animals. Although the geometric mean (90% CI) values of abiraterone AUC(last) in groups A-F were similar to the IIV group (24.36 (23.79-41.00) vs. 26.29 (20.56-47.00) mg/mL center dot min center dot g), the results generated in the isolated parallel groups provided imprecise estimates of the true AUC(last) values ranging from 9.62 to 44.62 mg/mL center dot min center dot g due to chance. Notably, in 4 out of 15 possible pair comparisons between the parallel groups, the confidence intervals did not include 100%, which is the true ratio for all comparisons tested after identical formulation administration to all groups. A cross-over design can significantly improve the methodology in short-term comparative pre-clinical pharmacokinetic studies, and can provide more precise and accurate results in comparison to more traditional pre-clinical study designs.

Název v anglickém jazyce

Pharmacokinetic Variability in Pre-Clinical Studies: Sample Study with Abiraterone in Rats and Implications for Short-Term Comparative Pharmacokinetic Study Designs

Popis výsledku anglicky

One of the major concerns for all in vivo experiments is intra- and inter-subject variability, which can be a great source of inaccuracy. The aim of this study is, therefore, to estimate the ability of parallel vs. cross-over design studies in order to describe the relative pharmacokinetic performance of the studied drug formulations. We analyzed the data from a drug development program that examined the performance of innovative abiraterone acetate formulations against the identical reference product in three stages. In stages 1-3, groups A-F were dosed with the reference product once in a parallel manner. Stage 4 was performed to evaluate the intra-individual variability (IIV) by repeated administration of the reference product to the same animals. Although the geometric mean (90% CI) values of abiraterone AUC(last) in groups A-F were similar to the IIV group (24.36 (23.79-41.00) vs. 26.29 (20.56-47.00) mg/mL center dot min center dot g), the results generated in the isolated parallel groups provided imprecise estimates of the true AUC(last) values ranging from 9.62 to 44.62 mg/mL center dot min center dot g due to chance. Notably, in 4 out of 15 possible pair comparisons between the parallel groups, the confidence intervals did not include 100%, which is the true ratio for all comparisons tested after identical formulation administration to all groups. A cross-over design can significantly improve the methodology in short-term comparative pre-clinical pharmacokinetic studies, and can provide more precise and accurate results in comparison to more traditional pre-clinical study designs.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Pharmaceutics [online]

ISSN

1999-4923

e-ISSN

1999-4923

Svazek periodika

14

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

9

Strana od-do

643

Kód UT WoS článku

000774272400001

EID výsledku v databázi Scopus

2-s2.0-85127205642