Skip to main content
Log in

Variability in the pharmacokinetics of epirubicin: a population analysis

  • Original Articles
  • Epirubicin, Population/Pharmacokinetics, Variability, NONNEM
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

Population pharmacokinetic analysis of the anticancer agent epirubicin was carried out using the program NONMEM. Data were available from 36 patients aged 20–73 years, of whom 23 were women. All subjects exhibited normal liver and renal function. Epirubicin was given as a short-term i. v. infusion over the dose range of 25–100 mg/m2, and an average of 11 plasma samples/subject were taken for a period of up to 72 h after each dose. A Two compartment model was fitted to the data, characterised by the parameters clearance, volume of the central compartment, alpha and beta. Clearance was tested as a linear function of various demographic and/or biochemical features. A significant proportion of the variability in clearance could be attributed to sex, and also to age in women. For example, a 25-year-old man would display an average clearance of 95 l/h, whereas a 70-year-old woman would exhibit an average clerance of 64 l/h. Such differences in clearance might be important in the selection of epirubicin dose regimens.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Beal SL, Sheiner LB (1979, 1989) NONMEM (user's guide), parts I–VI. Technical report. Division of Clinical Pharmacology, University of California, San Francisco

    Google Scholar 

  2. Camaggi CM, Strocchi E, Tamassia V, Martoni A, Giovannini M, Iafelice G, Canova N, Marraro D, Martini A, Pannuti F (1982) Pharmacokinetic studies of 4′-epi-doxorubicin in cancer patients with normal and impaired renal function and with hepatic metastases. Cancer Treat Rep 66:1819–1824

    Google Scholar 

  3. 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

    Google Scholar 

  4. Eksborg S (1989) Pharmacokinetics of anthracyclines. Acta Oncol 28:873–876

    Google Scholar 

  5. Evans WE, Relling MV (1989) Clinical pharmacokinetics-pharmacodynamics of anticancer drugs. Clin Pharmacokinet 16: 327–336

    Google Scholar 

  6. Evans WE, Crom WR, Abromowitch M, Dodge R, Look AT, Bowman P, George SL, Pui C-H (1986) Clinical pharmacodynamics of high-dose methotrexate in acute lymphocytic leukemia. N Engl J Med 314:417–477

    Google Scholar 

  7. Hartman N, Basseches PJ, Powis G (1982) Effect of cyclophosphamide pretreatment on the short-term disposition and biliary excretion of Adriamycin metabolites in the rat. Cancer Chemother Pharmacol 10:11

    Google Scholar 

  8. Hu OY-P, Chang S-P, Jame J-M, Chen K-Y (1989) Pharmacokinetic and pharmacodynamic studies with 4′-epi-doxorubicin in nasopharyngeal carcinoma patients. Cancer Chemother Pharmacol 24: 332–337

    Google Scholar 

  9. Israel M, Pegg WJ, Wilkinson PM, Garnick MB (1978) Liquid chromatographic analysis of Adriamycin and metabolites in biological fluids. J Liquid Chromatogr 1:795–809

    Google Scholar 

  10. Milano G, Namer M, Boublil J-L, Khater R, Frenay M, Thyss A, Bourry J, Philip C, Renee N, Bruneton J-N (1987) Relationship between systemic 5-FU passage and response in colorectal patients treated with interhepatic chemotherapy. Cancer Chemother Pharmacol 20:71–74

    Google Scholar 

  11. Natale N, Piazza E, Italia C, Trabattoni A, Luchini S (1983) The kinetics of anthracyclines in human plasma and tissues: daunomycin, doxorubicin and 4′-epidoxorubicin. Drugs Exp Clin Res IX: 775–779

    Google Scholar 

  12. Powis G (1985) Anticancer drug pharmacodynamics. Cancer Chemother Pharmacol 14:177–183

    Google Scholar 

  13. Robert J (1980) Extraction of anthracyclines from biological fluids for HPLC evaluation. J Liquid Chromatogr 3:1561–1572

    Google Scholar 

  14. Robert J, Vrignaud P, Nguyen-Ngoc T, Iliadis 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

    Google Scholar 

  15. Rodman JH, Abromowitch M, Sinkule JA, Hayes A, Rivera GK, Evans WE (1987) Clinical pharmacodynamics of continuous infusion teniposide — systemic exposure as a determinant of response in a phase I trial. J Clin Oncol 5:1007–1014

    Google Scholar 

  16. Sheiner LB, Rosenberg B, Marathe VV (1977) Estimation of population characteristics from routine clinical data. J Clin Oncol 5: 445–474

    Google Scholar 

  17. Tjuljandin SA, Doig RG, Sobol MM, Watson DM, Sheridan WP, Morstyn G, Mihaly G, Green MD (1990) Pharmacokinetics and toxicity of two schedules of high dose epirubicin. Cancer Res 50: 5095–5101

    Google Scholar 

  18. Vrignaud P, Eghball H, Hoerni B, Iliadis A, Robert J (1985) Pharmacokinetics and metabolism of epirubicin during repetitive courses of administration in Hodgkin's patients. Eur J Cancer Clin Oncol 21: 1307–1315

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wade, J.R., Kelman, A.W., Kerr, D.J. et al. Variability in the pharmacokinetics of epirubicin: a population analysis. Cancer Chemother. Pharmacol. 29, 391–395 (1992). https://doi.org/10.1007/BF00686009

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00686009

Keywords

Navigation