ArticlePharmaceutical research2001
Influence of P-glycoprotein modulators on cardiac uptake, metabolism, and effects of idarubicin.
Article in Pharmaceutical research, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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
3 citing papers in PubMed, 19 citations in OpenAlex.
- Myocardial pharmacokinetics of ebastine, a substrate for cytochrome P450 2J, in rat isolated heart.British journal of pharmacology · 2011Article
- Caffeine enhances myocardial uptake of idarubicin but reverses its negative inotropic effect.Naunyn-Schmiedeberg's archives of pharmacology · 2003Article
- Kinetic analysis of saturable myocardial uptake of idarubicin in rat heart: effect of doxorubicin and hypothermia.Pharmaceutical research · 2003Article
Corrections and comments
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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
purposeThe clinical utility of anthracyclines like idarubicin (IDA) is limited by the occurrence of multidrug resistance and cardiotoxicity. Previous studies have demonstrated that the multidrug transporter P-glycoprotein (P-gp) is present in the heart and have suggested that it exerts a protective function. We sought to determine the influence of P-gp inhibitors verapamil and PSC 833 on myocardial uptake, metabolism, and actions of IDA.
methodsIn Langendorff-perfused rat hearts, the outflow concentration-time curve and the residual amount in cardiac tissue of IDA and its active metabolite idarubicinol (IDOL) were measured after 0.5 mg dose of IDA in the absence and presence of the P-gp inhibitors verapamil and PSC 833.
resultsDuring perfusion (80 min), 2% of the IDA dose was converted to IDOL in the heart. Myocardial uptake of IDA was significantly increased by verapamil but not by PSC 833, which increased the recovery of IDA and IDOL. IDA significantly decreased left ventricular developed pressure to approximately 40% and increased coronary vascular resistance to 140% of baseline level, respectively. The vasoconstrictive effect was markedly potentiated by PSC 833.
conclusionsThe enhancement of myocardial IDA uptake by verapamil could be due to a decrease in P-gp-mediated efflux. PSC 833 inhibits cardiac metabolism (non-IDOL pathways) and increases the acute cardiotoxicity of IDA.
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