Logo Medical Science Monitor Basic Research

Call: 1.631.470.9640
Mon-Fri 10 am - 2 pm EST

Contact Us

Logo Medical Science Monitor Basic Research Logo Medical Science Monitor Basic Research Logo Medical Science Monitor Basic Research

04 November 2013 : Original article  

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

Josephine Tabea TauerABCDEF, Lorenz C. HofbauerACDEG, Rolang JungBDE, Reinhold G. ErbenABDEG, Meinolf SuttorpACDEG

DOI: 10.12659/MSMBR.889518

Med Sci Monit Basic Res 2013; 19:274-278


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 AND 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® micro-osmotic 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.

Keywords: Aniline Compounds - pharmacology, Aging, Bone Development - drug effects, Drug Delivery Systems - instrumentation, Femur - drug effects, Infusion Pumps, Implantable, Nitriles - pharmacology, Osmosis - drug effects, Protein Kinase Inhibitors - pharmacology, Quinolines - pharmacology, Rats, Wistar, Tibia - drug effects, Weight Gain - drug effects

Add Comment 0 Comments

571 1

Most Viewed Current Articles

05 Jan 2021 : Review article  

A Southeast Asian Perspective on the COVID-19 Pandemic: Hemoglobin E (HbE)-Trait Confers Resistance Against...

DOI :10.12659/MSMBR.929207

Med Sci Monit Basic Res 2021; 27:e929207

05 May 2022 : Laboratory Research  

Calcitriol Inhibits Proliferation and Potentially Induces Apoptosis in B16-F10 Cells

DOI :10.12659/MSMBR.935139

Med Sci Monit Basic Res 2022; 28:e935139

07 Jul 2022 : Laboratory Research  

Cytotoxicity, Apoptosis, Migration Inhibition, and Autophagy-Induced by Crude Ricin from Ricinus communis S...

DOI :10.12659/MSMBR.936683

Med Sci Monit Basic Res 2022; 28:e936683

09 Jun 2021 : Laboratory Research  

Vitamin D Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in A549 Cells by Downregulating Inflammato...

DOI :10.12659/MSMBR.931481

Med Sci Monit Basic Res 2021; 27:e931481

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416