Increased accumulation of doxorubicin and doxorubicinol in cardiac tissue of mice lacking mdr1a P-glycoprotein
1999
Doxorubicin Accumulation in Mice Without P-glycoprotein
publication
Author Information
Author(s): Asperen J van, Tellingen O van, Tijssen F, Schinkel A H, Beijnen J H
Primary Institution: The Netherlands Cancer Institute
Hypothesis
The absence of mdr1a P-glycoprotein affects the pharmacokinetics of doxorubicin.
Conclusion
Mice lacking mdr1a P-glycoprotein showed increased accumulation of doxorubicin in cardiac tissue, which may raise the risk of cardiotoxicity.
Supporting Evidence
- Doxorubicin's half-life and area under the curve were higher in mdr1a(–/–) mice.
- Doxorubicin and doxorubicinol accumulated more in the hearts of mdr1a(–/–) mice.
- Increased drug accumulation was also observed in the brain and liver of mdr1a(–/–) mice.
Takeaway
When mice don't have a certain protein, a cancer drug called doxorubicin stays in their hearts longer, which could be risky.
Methodology
Doxorubicin was given to mice, and its levels were measured in plasma, tissues, urine, and feces using high-performance liquid chromatography.
Participant Demographics
Study involved mdr1a(–/–) and wild-type mice.
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website