Summary
Thirteen cancer patients were studied following a total of 41 courses of epirubicin (EPI) (38–50 mg·m−2, mean 49.2 mg·m−2, administered by a 60 min infusion), together with other cancer chemotherapeutic agents. The aim was to consider the disposition of EPI and metabolites following subsequent courses as it has been reported that doxorubicin (the 4′-epimer parent of EPI) clearance is increased following the first administration.
We have observed that EPI-glucuronide accounted for a mean 78.0%, epirubicinol 0.2% and epirubicinol-glucuronide 19.3% and that parent EPI accounted for only 2.4% of the EPI-compounds measured (mean of all patients and courses) for the 3 h period immediately following the infusion.
These data confirm the rapid metabolism of EPI and the dominance of the glucuronidation metabolite pathway (which is not available to doxorubicin) and are compared with the metabolite profile observed in other reports.
Large inter- and intra-individual variability in area under the plasma concentration/time curve were observed with no clear evidence of any consistent directional trend for such fluctuations, suggesting that factors contributing to EPI disposition are multivariate.
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Camaggi CM, Comparsi R, Strocchi E, Testoni F, Angelilli B, Pannuti F (1988) Epirubicin and doxorubicin comparative metabolism and pharmacokinetics. Cancer Chemother Pharmacol 21: 221–228
Cersosimo RJ, Hong WK (1986) Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue. J Clin Oncol 4: 425–439
Gessner T, Roberts J, Bolanowska W, Hoerni B, Durand M, Priesler H, Rustum J (1981) Effects of prior therapy on plasma levels of adriamycin during subsequent therapy. J Med 12: 183–193
Morris RG, Reece PA, Dale BM, Green RM, Kotasek D, Saccoia NC, Sage RE (1989) Alteration in doxorubicin and doxorubicinol plasma concentrations with repeated courses to patients. Ther Drug Monit 11: 380–383
Mross K, Maessen P, van der Vijgh WJF, Gall H, Boven E, Pinedo HM (1988) Pharmacokinetics and metabolism of epidoxirubicin and doxorubicin in humans. J Clin Oncol 6: 517–526
Preisler HD, Gessner T, Azarnia N et al. (1984) Relationship between plasma adriamycin levels and the outcome of remission induction therapy for acute nonlymphocytic leukemia. Cancer Chemother Pharmacol 12: 125–130
Robert J, Hoerni B, Vrignaud P, Lagarde C (1983) Early-phase pharmacokinetics of doxorubicin in non-Hodgkin's lymphoma patients. Cancer Chemother Pharmacol 10: 115–119
Robert J, Vrignaud P, Nguyen-Ngoc T, Lliadis A, Mauriac L, Hurteloup P (1985) Comparative pharmacokinetics and metabolism of doxorubicin and epirubicin in patients with metastatic breast cancer. Cancer Treat Rep 69: 633–640
Tomlinson E, Malspeis L (1982) Concomitant adsorption and stability of some anthracycline antibiotics. J Pharm Sci 71: 1121–1125
Weenen H, van Maanen MS, de Planque MM, McVie JG, Pindeo HM (1984) Metabolism of 4′-modified analogs of doxorubicin. Unique glucuronidation pathway for 4′-epidoxorubicin. Eur J Cancer Clin Oncol 20: 919–926
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Morris, R.G., Kotasek, D. & Paltridge, G. Disposition of epirubicin and metabolites with repeated courses to cancer patients. Eur J Clin Pharmacol 40, 481–487 (1991). https://doi.org/10.1007/BF00315227
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DOI: https://doi.org/10.1007/BF00315227