Evaluation of Pharmacokinetics of a BCS Class III Drug with Two Different Study Designs: Tenofovir Alafenamide Monofumarate Film-coated Tablet.
PBPK
bioequivalence
highly-variable drugs
pharmacokinetics
tenofovir alafenamide
Journal
AAPS PharmSciTech
ISSN: 1530-9932
Titre abrégé: AAPS PharmSciTech
Pays: United States
ID NLM: 100960111
Informations de publication
Date de publication:
30 May 2024
30 May 2024
Historique:
received:
21
02
2024
accepted:
08
05
2024
medline:
31
5
2024
pubmed:
31
5
2024
entrez:
30
5
2024
Statut:
epublish
Résumé
Tenofovir alafenamide (TAF) is a BCS Class III compound and an oral pro-drug of Tenofovir (TFV) with limited oral bioavailability. The bioavailability of the oral intake increases with food as a result of the low stability of the active substance in the stomach. The reference drug is "Vemlidy® 25 mg Film Tablet", which contains 25 mg of TAF in "hemifumarate" form, is under patent protection until 15.08.2032 by Gilead, and so the "monofumarate" form was used in the present study. At first, a pilot study was conducted involving 12 subjects under fed conditions. The results of the pilot study revealed the test and reference products were not bioequivalent, as a result of insufficient statistical power and high inter-subject variability. Secondly, a physiologically based pharmacokinetic (PBPK) simulation was performed based on the pilot study results and literature data. Finally, the power of the design was increased and the pivotal study design was optimized into a four-period, full-replicated, cross-over study with 34 subjects under fed conditions and it was concluded that the test and reference products were bioequivalent. In conclusion, the present study proved the importance of a correct study design with higher statistical power for a BCS Class III compound with high variability, to present the pharmacokinetics.
Identifiants
pubmed: 38816624
doi: 10.1208/s12249-024-02835-5
pii: 10.1208/s12249-024-02835-5
doi:
Substances chimiques
Tenofovir
99YXE507IL
Tablets
0
Alanine
OF5P57N2ZX
tenofovir alafenamide
EL9943AG5J
Adenine
JAC85A2161
Prodrugs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
123Informations de copyright
© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.
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