Evaluation of Pharmacokinetics of a BCS Class III Drug with Two Different Study Designs: Tenofovir Alafenamide Monofumarate Film-coated Tablet

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...

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Bibliographic Details
Published in:AAPS PharmSciTech 2024-05, Vol.25 (5), p.123, Article 123
Main Authors: Arısoy, Mustafa, Saydam, Mehtap, Dolaksız, Yasemin Ekin, Demirbaş, Özge, Talay, Çağrı, Sağlam, Onursal, Demiray, Gökçe, Kurtoğlu, Emel Doğan, Oktay, Ayşe Nur
Format: Article
Language:English
Subjects:
Adenine - administration & dosage
Adenine - analogs & derivatives
Adenine - pharmacokinetics
Administration, Oral
Adult
Alanine - chemistry
Alanine - pharmacokinetics
Biochemistry
Biological Availability
Biomedical and Life Sciences
Biomedicine
Biotechnology
Cross-Over Studies
Humans
Male
Pharmacology/Toxicology
Pharmacy
Pilot Projects
Prodrugs - administration & dosage
Prodrugs - pharmacokinetics
Research Article
Tablets
Tenofovir - administration & dosage
Tenofovir - analogs & derivatives
Tenofovir - pharmacokinetics
Therapeutic Equivalency
Young Adult
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Summary: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. Graphical Abstract
ISSN:1530-9932
1530-9932
DOI:10.1208/s12249-024-02835-5