Micro-osmotic pumps for continuous release of the tyrosine kinase inhibitor bosutinib in juvenile rats and its impact on bone growth
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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
Original language | English |
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Pages (from-to) | 274-278 |
Number of pages | 5 |
Journal | Medical Science Monitor |
Volume | 19 |
Publication status | Published - 2013 |
Peer-reviewed | Yes |
External IDs
PubMed | 24185529 |
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ORCID | /0000-0002-8691-8423/work/169175632 |
Keywords
ASJC Scopus subject areas
Keywords
- Bone, Bosutinib, Micro-osmotic pump, TKI (tyrosine kinase inhibitor)