PMID: 9180163May 29, 1997Paper

Reversal activity of cyclosporin A and its metabolites M1, M17 and M21 in multidrug-resistant cells

International Journal of Cancer. Journal International Du Cancer
G ToffoliM Boiocchi

Abstract

Cyclosporin A (CSA) is an effective inhibitor of the P-glycoprotein (P-gp) activity and has been shown to modulate multidrug resistance (MDR) in in vitro experimental models. During degradation of CSA, the metabolites arising from the parental compound reach high levels in the serum of patients, and it is not clear whether these metabolites maintain the reversal activity of the parental compound, like the metabolites of verapamil. In an in vitro experimental model, we compared the reversal activity of CSA and 3 CSA metabolites (M1, M17, and M21) in the range of concentrations obtained in whole blood during a clinical trial with CSA used as a revertant agent. As experimental model we used LoVo-resistant cells. Our in vitro studies indicated that the metabolic hydroxylation and demethylation of CSA lead to molecules that greatly differ from the parent drug in their reversal activity. In the range of concentration detected in the whole blood of the patients (1-3 microM), CSA had a significant reversal activity. It decreased the IC50 of antineoplastic drugs involved in MDR (vincristine, taxol, doxorubicin and etoposide) but not the IC50 of platinum or methotrexate. CSA increased intracellular doxorubicin content and inhibited P-gp ...Continue Reading

References

Nov 11, 1976·Biochimica Et Biophysica Acta·R L Juliano, V Ling
Jan 1, 1992·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M Boiocchi, G Toffoli
Oct 1, 1992·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A M YahandaB I Sikic
Apr 1, 1991·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C J RodenburgJ Verweij
Feb 1, 1991·Clinical Biochemistry·R W YatscoffL D Bowers
Nov 1, 1990·Therapeutic Drug Monitoring·K R CopelandR W Yatscoff
May 15, 1990·International Journal of Cancer. Journal International Du Cancer·R PirkerH Ludwig
Jan 18, 1989·Journal of the National Cancer Institute·L J GoldsteinG M Brodeur
Dec 20, 1989·Journal of the National Cancer Institute·G J SchuurhuisJ Lankelma
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·A R Safa
Feb 15, 1988·International Journal of Cancer. Journal International Du Cancer·A GruberP Reizenstein
Jun 1, 1995·American Journal of Clinical Oncology·E WarnerK L Skorecki

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Citations

Jul 5, 2005·Expert Opinion on Investigational Drugs·F Loor
Jul 1, 2010·Journal of Biomedical Research·Wujun XueXiaohui Tian
Jul 17, 2010·European Journal of Pharmacology·Olga WesołowskaKrystyna Michalak
Jun 19, 2008·Familial Cancer·Elaine AndersonDorothy Young

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