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The influence of partial hepatectomy on the pharmacokinetics of preoperatively injected 4′-epidoxorubicin in rats

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Summary

Preoperative administration of 4′-epidoxorubicin (Epi-A) has been suggested as adjuvant therapy in patients undergoing liver resection for hepatocarcinoma. To assess the influence of partial hepatectomy on the pharmacokinetics of Epi-A, an experimental study in rats was undertaken in which 5 mg/kg Epi-A was given i.v. 10 min prior to a 2/3 hepatic resection or sham operation. Epi-A levels in liver tissue and plasma were determined using a sensitive and specific HPLC method. A marked uptake of Epi-A in liver tissue was found at 10 min after injection. The partially hepatectomized rats showed a 2-fold increase in AUC between 4 and 72 h as compared with the shamoperated controls. The terminal half-life from 24 to 72 h was not significantly changed by the partial hepatectomy. The plasma binding of Epi-A was measured at 4 h post-surgery. The fraction of unbound Epi-A was 0.16 in partially hepatectomized animals and 0.20 in sham-operated rats. The results indicate that when Epi-A is given prior to liver resection, a dose reduction might be necessary to avoid increased side effects due to the rise in AUC.

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References

  1. Adson MA, Weiland LH (1981) Resection of primary solid hepatic tumors. Am J Surg 141: 18

    Article  PubMed  CAS  Google Scholar 

  2. Brauer RW (1963) Liver circulation and function. Physiol Rev 43: 115

    PubMed  CAS  Google Scholar 

  3. Broggini M, Colombo T, Martini A, Donelli MG (1980) Studies on the comparative distribution and biliary excretion of doxorubicin and 4′-epi-doxorubicin in mice and rats. Cancer Treat Rep 64: 897

    PubMed  CAS  Google Scholar 

  4. Eksborg S, Ehrsson H, Andersson I (1979) Reversed-phase liquid chromatographic determination of plasma levels of Adriamycin and Adriamycinol. J Chromatogr 164: 479

    Article  PubMed  CAS  Google Scholar 

  5. Eksborg S, Ehrsson H, Ekqvist B (1982) Protein binding of anthraquinone glycosides, with special reference to Adriamycin. Cancer Chemother Pharmacol 10: 7

    Article  PubMed  CAS  Google Scholar 

  6. Falkson G, Moertel CG, Lavin P, Pretorius FJ, Carbone PP (1978) Chemotherapy studies in primary liver cancer. Cancer 42: 2149

    Article  PubMed  CAS  Google Scholar 

  7. Foster JH (1970) Survival after liver resection for cancer. Cancer 26: 493

    Article  PubMed  CAS  Google Scholar 

  8. Higgins GM, Anderson RM (1931) Experimental pathology of the liver. Arch Pathol 12: 186

    Google Scholar 

  9. Hochster HS, Green MD, Speyer J, Fazzini E, Blum R, Muggia FM (1985) 4′-Epidoxorubicin (epirubicin): activity in hepatocellular carcinoma. J Clin Oncol 3: 1535

    PubMed  CAS  Google Scholar 

  10. Holton CP, Burrington JD, Hatch EI (1975) A multiple chemotherapeutic approach to the management of hepatoblastoma. Cancer 35: 1083

    Article  PubMed  CAS  Google Scholar 

  11. Islami AH, Pack GT (1959) Demonstration of liver regeneration by splenoportal venography. Am J Roentgenol 81: 855

    CAS  Google Scholar 

  12. Israel M, Pegg WJ, Wilkinson PM, Garnick MB (1978) Liquid chromatographic analysis of Adriamycin and metabolites in biological fluids. J Liquid Chromatogr 1: 795

    Article  CAS  Google Scholar 

  13. Lin TY (1970) Primary cancer of the liver. Scand J Gastroenterol [Suppl] 6: 223

    CAS  Google Scholar 

  14. Maessen PA, Mross KB, Pinedo HM, Van der Vijgh WJF (1987) Metabolism of epidoxorubicin in animals: absence of glucuronidation. Cancer Chemother Pharmacol 20: 85

    Article  PubMed  CAS  Google Scholar 

  15. Mross K, Maessen P, Van er Vijgh WJF, Gall H, Boven E, Pinedo HM (1988) Pharmacokinetics and metabolism of epidoxorubicin and doxorubicin in humans. J Clin Oncol 6: 517

    PubMed  CAS  Google Scholar 

  16. Nerenstone S, Friedman M (1987) Medical treatment of hepatocellular carcinoma. Gastroenterol Clin North Am 16: 603

    PubMed  CAS  Google Scholar 

  17. Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, Nakajima Y, Ohnishi K (1985) Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Cancer 56: 918

    Article  PubMed  CAS  Google Scholar 

  18. Patt YZ, Claghorn L, Charnsangavej C, Soski M, Cleary K, Mavligit GM (1988) Hepatocellular carcinoma. Cancer 61: 1884

    Article  PubMed  CAS  Google Scholar 

  19. Robert J (1980) Extraction of anthracyclines from biological fluids for HPLC evaluation. J Liquid Chromatogr 3: 1561

    Article  CAS  Google Scholar 

  20. Rose LM, Tillery KF, El Dareer SM, Hill DL (1988) Highperformance liquid chromatographic determination of doxorubicin and its metabolites in plasma and tissue. J Chromatogr 425: 419

    Article  PubMed  CAS  Google Scholar 

  21. Strocchi E, Camaggi CM, Rossi AP, Angelelli B, Comparsi R, Franchini A, Del Prete P, Cola B, Pannuti F (1985) Epirubicin pharmacokinetics after intrahepatic arterial and intraperitoneal administration. Drugs Exp Clin Res 11: 295

    PubMed  CAS  Google Scholar 

  22. Weenen H, Lankelma J, Penders PGM, McVie JG, Ten Bokkel Huinink WW, Planque MM de, Pinedo HM (1983) Pharmacokinetics of 4′-epidoxorubicin in man. Invest New Drugs 1: 59

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Pharmacology, University of Oslo, Rikshospitalet, N-0027, Oslo 1, Norway

    Kirsten Sundby Hall & Hans Erik Rugstad

  2. Institute of Clinical Biochemistry, University of Oslo, Rikshospitalet, N-0027, Oslo 1, Norway

    Liv Endresen

  3. Experimental Animal Department, University of Oslo, Rikshospitalet, N-0027, Oslo 1, Norway

    Leif Schjerven

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  1. Kirsten Sundby Hall
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  2. Liv Endresen
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  3. Leif Schjerven
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  4. Hans Erik Rugstad
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Hall, K.S., Endresen, L., Schjerven, L. et al. The influence of partial hepatectomy on the pharmacokinetics of preoperatively injected 4′-epidoxorubicin in rats. Cancer Chemother Pharmacol 26, 444–448 (1990). https://doi.org/10.1007/BF02994096

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  • DOI: https://doi.org/10.1007/BF02994096

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