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Lack ofin vitro interactions using human liver micro-somes between rabeprazole and anticancer drugs

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Summary

The potential interactions between rabeprazole, a widely used proton pump inhibitor, and anticancer drugs (5-fluorouracil, docetaxel, cyclophosphamide, gemcitabine, methotrexate, doxorubicin, etoposide) or drugs commonly present in the therapy of oncological patients (fluoxetine and ondansetron), were studied using in vitro human liver microsomes. The interactions between rabeprazole and the anticancer drugs were evaluated by measuring their concentrations in test and control incubations with HPLC-DAD-UV methods. To achieve this aim, nine HPLC-DAD-UV methods were developed using different stationary and mobile phases. The methods were then validated for the following parameters: selectivity, linearity, precision, and accuracy. As expected rabeprazole did not significantly inhibit the metabolism of the evaluated drugs in human liver microsomal preparations at the selected concentrations. These results shows that rabeprazole probably could be devoid of pharmacokinetic interactions with common drugs used during chemotherapy.

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References

  1. Ishizaki T., Horai Y. (1999). Cytochrome P450 and the metabolism of proton pump inhibitors-emphasis on rabeprazole. Aliment. Pharmacol. Ther., 13, 27–36.

    Article  CAS  PubMed  Google Scholar 

  2. Yasuda S., Horai Y., Tomono Y., Nokai H., Yamato C., Manabe K., Kobayashi K., Chiba K., Ishizaki T. (1995). Comparison of the kinetic disposition and metabolism of E3810, a new proton pump inhibitor, and omeprazole in relation toS-mephenytoin 4′-hydroxylation status. Clin. Pharmacol. Therapy, 58, 143–154.

    Article  CAS  Google Scholar 

  3. VandenBranden M., Ring B.J., Binkley S.N., Wrighton S.A. (1996). Interaction of human liver cytochromes P450 in vitro with LY307640, a gastric proton pump inhibitor. Pharmacogenetics, 6, 81–91.

    Article  CAS  PubMed  Google Scholar 

  4. Klotz U. (2000). Pharmacokinetic considerations in the eradication of Helicobacter pylori. Clin. Pharmacokinet, 38, 243–270.

    Article  CAS  PubMed  Google Scholar 

  5. Royer I., Monsarrat B., Sonnier M., Wright M., Crested T. (1996). Metabolism of docetaxel by human cytochromes P450: interactions with paclitaxel and other antineoplastic drugs. Cancer Res., 56, 58–65.

    CAS  PubMed  Google Scholar 

  6. Vaclavikova R., Soucek P., Svobodova L., Anzenbacher P., Simek P., Guengerich F.P., Gut I. (2004). Different in vitro metabolism of paclitaxel and docetaxel in humans, rats, pigs, and minipigs. Drug Metab. Dispos., 32, 666–74.

    Article  CAS  PubMed  Google Scholar 

  7. Relling M.V., Nemec J., Schuetz E.G. Schuetz J.D., Gonzalez F.J., Korzekwa K.R. (1994).O-demethylation of epipodophyllotoxins is catalyzed by human cytochrome P450 3A4. Mol. Pharmacol., 45, 352–358.

    CAS  PubMed  Google Scholar 

  8. Kawashiro T., Yamashita K., Zhao X.J., Koyama E., Tani M., Chiba K., Ishizaki T. (1998). A study on the metabolism of etoposide and possible interactions with antitumor or sup porting agents by human liver microsomes. J. Pharmacol. Exp. Ther., 286, 1294–1300.

    CAS  PubMed  Google Scholar 

  9. Chang T.K.H., Weber C.F., Crespi C.L., Waxman D.J. (1993). Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes. Cancer Res., 53, 5629–5637

    CAS  PubMed  Google Scholar 

  10. Ren S., Yang J.S., Kalhorn T.F., Slattery J.T. (1997). Oxidation of cyclophosphamide to 4-hydroxycyclophosphamide in human liver microsomes. Cancer Res., 57, 4229–4235.

    CAS  PubMed  Google Scholar 

  11. Huang Z., Roy P., Waxman D.J. (2000). Role of human liver microsomal CYP3A4 and CYP2B6 in catalyzingN-de-chloroethylation of cyclophosphamide and ifosfamide. Biochem. Pharmacol., 59, 961–972.

    Article  CAS  PubMed  Google Scholar 

  12. Mandrioli R., Cantelli Forti G., Raggi M.A., (2006). Fluoxetine Metabolism and Pharmacological Interactions: The Role of Cytochrome P450. Curr. Drug Metab., 7, 127–133 and references cited herein.

    Article  CAS  PubMed  Google Scholar 

  13. Dixon C.M., Colthup P.V., Serabjit-Singh C.J., Kerr B.M., Boehlert C.C., Park G.R., Tarbit M.H. (1995). Multiple forms of cytochrome P450 are involved in metabolism of ondansetron in humans. Drug Metab. Dispos., 23, 1225–1230.

    CAS  PubMed  Google Scholar 

  14. Chladek J., Martinkova J., Sispera L. (1997). Anin vitro study on methotrexate hydroxylation in rat and human liver. Physiol. Res., 46, 371–379.

    CAS  PubMed  Google Scholar 

  15. Diasio R.B., Harris B.E. (1989). Clinical pharmacology of 5-fluorouracil. Clin. Pharmacokinet., 16, 215–37.

    Article  CAS  PubMed  Google Scholar 

  16. Giovannetti E., Mey V., Loni L., Nannizzi S., Barsanti G., Savarino G., Ricciardi S., Del Tacca M., Danesi R. (2007). Cytotoxic activity of gemcitabine and correlation with expression profile of drug-related genes in human lymphoid cells. Pharmacol. Res., 55, 343–349.

    Article  CAS  PubMed  Google Scholar 

  17. 17. De Jong J., Geijssen G.J., Munniksma C.N., Vermorken J.B., Van der Vijgh W.J. (1992): Plasma pharmacokinetics and pharmacodynamics of a new prodrugN-1-leucyldoxorubicin and its metabolites in a phase I clinical trial. J. Clin. Oncol., 10, 1897–1906.

    PubMed  Google Scholar 

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Tamaro, I., Genazzani, A., Canonico, P. et al. Lack ofin vitro interactions using human liver micro-somes between rabeprazole and anticancer drugs. Eur. J. Drug Metabol. Pharmacokinet. 34, 19–26 (2009). https://doi.org/10.1007/BF03191379

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  • DOI: https://doi.org/10.1007/BF03191379

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