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Peer-reviewedCC BY 4.0Disease Models & Mechanisms

Pharmacokinetics and efficacy of tank-water-administered dabrafenib, a BRAF inhibitor, in a zebrafish model of melanoma

  • Jenna Villman1
  • Nikol Dibus1,2
  • Jonas Huhn3
  • Anna-Mari Haapanen-Saaristo1
  • Ilia Evstafev1
  • Alex M. Dickens1
  • Oliver Scherf-Clavel3
  • Ilkka Paatero1
  • Kari J. Kurppa1,2
  1. 1Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland
  2. 2Institute of Biomedicine and Medicity Research Laboratory, University of Turku, 20520 Turku, Finland
  3. 3Ludwig-Maximilians-Universität München, Department of Pharmacy, 81377 Munich, Germany
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Abstract

Zebrafish models are widely used to study BRAF-mutant melanoma biology. However, long-term treatment of adult fish with small-molecule BRAF inhibitors remains challenging, and pharmacokinetic data to inform rational dosing strategies are largely lacking for most small molecules in zebrafish. Here, we assessed the pharmacokinetics, metabolism and efficacy of continuously tank-water-administered dabrafenib, a BRAF inhibitor, in adult zebrafish. Dabrafenib was rapidly absorbed from tank water, reaching efficacious plasma levels within 1 h, but also showed fast elimination kinetics with a half-life of 1.0 h. Most human metabolites of dabrafenib were detected in zebrafish, suggesting conserved metabolic processes. Continuous tank-water administration achieved therapeutically relevant steady-state dabrafenib plasma levels that inhibited BRAF-driven signaling and produced robust efficacy in vivo in a genetic zebrafish model of BRAF-mutant melanoma without apparent toxicity. Together, these results demonstrate that continuous tank-water administration of dabrafenib is a feasible, efficient and well-tolerated dosing strategy in zebrafish melanoma models, and may facilitate dosing of other small-molecule inhibitors, especially those with a short in vivo half-life in zebrafish.

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Cite

BibTeXRIS
BibTeX
@article{villman2026pharmacokinetics,
  title = {{Pharmacokinetics and efficacy of tank-water-administered dabrafenib, a BRAF inhibitor, in a zebrafish model of melanoma}},
  author = {Jenna Villman and Nikol Dibus and Jonas Huhn and Anna-Mari Haapanen-Saaristo and Ilia Evstafev and Alex M. Dickens and Oliver Scherf-Clavel and Ilkka Paatero and Kari J. Kurppa},
  journal = {Disease Models \& Mechanisms},
  year = {2026},
  month = oct,
  doi = {10.1242/dmm.052907},
  url = {https://doi.org/10.1242/dmm.052907},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Pharmacokinetics and efficacy of tank-water-administered dabrafenib, a BRAF inhibitor, in a zebrafish model of melanoma
AU  - Jenna Villman
AU  - Nikol Dibus
AU  - Jonas Huhn
AU  - Anna-Mari Haapanen-Saaristo
AU  - Ilia Evstafev
AU  - Alex M. Dickens
AU  - Oliver Scherf-Clavel
AU  - Ilkka Paatero
AU  - Kari J. Kurppa
PY  - 2026
DA  - 2026/10/16
JO  - Disease Models & Mechanisms
DO  - 10.1242/dmm.052907
UR  - https://doi.org/10.1242/dmm.052907
AB  - Zebrafish models are widely used to study BRAF-mutant melanoma biology. However, long-term treatment of adult fish with small-molecule BRAF inhibitors remains challenging, and pharmacokinetic data to inform rational dosing strategies are largely lacking for most small molecules in zebrafish. Here, we assessed the pharmacokinetics, metabolism and efficacy of continuously tank-water-administered dabrafenib, a BRAF inhibitor, in adult zebrafish. Dabrafenib was rapidly absorbed from tank water, reaching efficacious plasma levels within 1 h, but also showed fast elimination kinetics with a half-life of 1.0 h. Most human metabolites of dabrafenib were detected in zebrafish, suggesting conserved metabolic processes. Continuous tank-water administration achieved therapeutically relevant steady-state dabrafenib plasma levels that inhibited BRAF-driven signaling and produced robust efficacy in vivo in a genetic zebrafish model of BRAF-mutant melanoma without apparent toxicity. Together, these results demonstrate that continuous tank-water administration of dabrafenib is a feasible, efficient and well-tolerated dosing strategy in zebrafish melanoma models, and may facilitate dosing of other small-molecule inhibitors, especially those with a short in vivo half-life in zebrafish.
SN  - 1754-8403
SN  - 1754-8411
ER  -