Impact of Splitting or Crushing on the Relative Bioavailability of the Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen
| Autor: | Ceyhun Bicer, Richard Bruce Simonson, Michael Reeder, Herta Crauwels, Richard E. Nettles, Kimberley Brown, David P. Thomas, Kevin McKenney |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Cmax Pharmaceutical Science Biological Availability Pharmacology Emtricitabine 030226 pharmacology & pharmacy Tenofovir alafenamide 03 medical and health sciences Young Adult 0302 clinical medicine Pharmacokinetics medicine Humans Pharmacology (medical) Tenofovir Darunavir Alanine Cross-Over Studies business.industry Cobicistat Adenine Middle Aged Crossover study Healthy Volunteers Bioavailability Drug Combinations 030220 oncology & carcinogenesis Linear Models Female business medicine.drug Tablets |
| Zdroj: | Clinical pharmacology in drug development. 8(4) |
| ISSN: | 2160-7648 |
| Popis: | Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is an oral once-daily single-tablet regimen for the treatment of human immunodeficiency virus-1 infection. Different administration modalities for the D/C/F/TAF fixed-dose combination tablet were explored in this phase 1 randomized, open-label, 3-period, 3-treatment crossover study enrolling 30 healthy adults. The primary objective was to assess the relative bioavailability of each component after a single dose of D/C/F/TAF (800/150/200/10 mg) administered as a split or crushed tablet (tests) versus swallowed whole (reference). Pharmacokinetic parameters (noncompartmental analysis; logarithm-transformed) for each component were compared using linear mixed-effects modeling. For the split versus whole tablet, the bioavailabilities (maximum plasma concentration [Cmax ] and area under the plasma concentration-time curve [AUClast ]) of each D/C/F/TAF component were comparable. For the crushed versus whole tablet, the bioavailabilities of darunavir, cobicistat, and emtricitabine were comparable, except for a 17% decrease in emtricitabine Cmax ; the relative bioavailability of tenofovir alafenamide decreased by 29% and 19% for Cmax and AUClast , respectively. All intakes were safe and generally well tolerated. In summary, there was no clinically relevant impact on the bioavailability of D/C/F/TAF components when administered as a split tablet compared with a tablet swallowed whole. Administration of a crushed tablet resulted in a modest decrease in tenofovir alafenamide bioavailability; the clinical relevance of this change has not been assessed but is expected to be minimal based on the wide therapeutic window for this agent. |
| Databáze: | OpenAIRE |
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