ArticlePharmaceutical research2003
Kinetic analysis of saturable myocardial uptake of idarubicin in rat heart: effect of doxorubicin and hypothermia.
Article in Pharmaceutical research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed, 9 citations in OpenAlex.
- Modeling cardiac uptake and negative inotropic response of verapamil in rat heart: effect of amiodarone.Pharmaceutical research · 2007Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeLittle is known of how anthracyclines are transported into the heart. Our previous kinetic study suggested saturable myocardial uptake of idarubicin. This study sought to determine the effects of temperature reduction and of doxorubicin coadministration on the transport process.
methodsIn Langendorff-perfused rat hearts, a 0.5 mg dose of idarubicin was infused over 10 min. The outflow concentration-time curve as well as the residual amounts in cardiac tissue of idarubicin and its active metabolite idarubicinol were measured after temperature reduction (from 37 degrees C to 30 degrees C) and in the presence of doxorubicin (20 microM) in the perfusate. The outflow concentration-time profile of idarubicin was analyzed by a four-compartment model and simultaneous nonlinear regression.
resultsDoxorubicin significantly inhibited the Michaelis-Menten-like uptake process of idarubicin in the heart (50% decrease in Vmax), leading to a decreased net tissue uptake of idarubicin. Kinetic analysis of sensitivity to temperature reduction revealed a 2.6-fold increase in KM; however, this inhibition of idarubicin uptake was counterbalanced by a decrease in efflux rate.
conclusionsThese data confirm the existence of a saturable myocardial uptake mechanism for idarubicin and might provide useful information for optimizing anthracycline dosage regiments.
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