Pharmacokinetic Variability in Pre-Clinical Studies: Sample Study with Abiraterone in Rats and Implications for Short-Term Comparative Pharmacokinetic Study Designs
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216208:11110/22:10443335 RIV/00216208:11310/22:10443335
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Pharmacokinetic Variability in Pre-Clinical Studies: Sample Study with Abiraterone in Rats and Implications for Short-Term Comparative Pharmacokinetic Study Designs
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
—
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Pharmaceutics [online]
ISSN
1999-4923
e-ISSN
1999-4923
Volume of the periodical
14
Issue of the periodical within the volume
3
Country of publishing house
CH - SWITZERLAND
Number of pages
9
Pages from-to
643
UT code for WoS article
000774272400001
EID of the result in the Scopus database
2-s2.0-85127205642