Micro-osmotic pumps for continuous release of the tyrosine kinase inhibitor bosutinib in juvenile rats and its impact on bone growth

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

Background: Bosutinib is a third-generation dual tyrosine kinase inhibitor (TKI) inhibiting Abl and Src kinases. It was developed to act on up-regulated tyrosine kinases (TKs) like BCR-ABL in Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) when resistance to first-and second-generation TKIs developed. However, first-and second-generation TKIs show off-target effects on bone metabolism, whereas studies on skeletal adverse effects of bosutinib are still lacking. Therefore, it was the aim of this study to continuously expose juvenile rats to bosutinib and to analyze its influence on the growing bone. Material/Methods: Starting after weaning, 4-week-old Wistar rats were chronically exposed over a 28-day period to varying concentrations of bosutinib, which were continuously administered subcutaneously via implanted Alzet® microosmotic pumps. After necropsy, the length of the femora and tibiae were analyzed. Results: Continuous administration of bosutinib by micro-osmotic pumps led to serum drug levels in the lower therapeutic range, was well tolerated, and exhibited only minor adverse effects on the growing skeleton. Conclusions: Micro-osmotic pumps represent a convenient system for continuous TKI release in young growing rats. Compared to first- and second-generation TKIs, bosutinib seems to exert fewer adverse effects on the growing bone.

Details

OriginalspracheEnglisch
Seiten (von - bis)274-278
Seitenumfang5
FachzeitschriftMedical Science Monitor
Jahrgang19
PublikationsstatusVeröffentlicht - 2013
Peer-Review-StatusJa

Externe IDs

PubMed 24185529
ORCID /0000-0002-8691-8423/work/169175632

Schlagworte

ASJC Scopus Sachgebiete

Schlagwörter

  • Bone, Bosutinib, Micro-osmotic pump, TKI (tyrosine kinase inhibitor)