Summary
The plasma pharmacokinetics of adriamycin and 4'epi-adriamycin have been studied in 6 patients with ovarian carcinoma after simultaneous intravenous administration of equal amounts of the two anthracyclines. A highly selective liquid chromatographic analytical method permitted quantification of plasma concentrations of the two drugs as well as their corresponding 13-hydroxy metabolites.
The plasma concentrations of each drug followed a three-compartment open model, with great interindividual variation in the pharmacokinetic parameters. On average, the area under the plasma concentration time curve (AUC) and the maximum plasma concentration (Cmax) were 1.6- and 1.2-times larger for adriamycin than for 4'epi-adriamycin. 4'Epi-adriamycin was eliminated faster than adriamycin by 4 of the 6 patients, the average terminal half-life of the latter being 1.4-times longer.
The plasma concentrations of the 13-hydroxy metabolites did not exceed 20 ng/ml. Their AUC values averaged 23% of those of the intact drugs.
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References
Blum RH, Carter SK (1974) Adriamycin. A new anticancer drug with significant clinical activity. Ann Int Med 80: 249–259
Carter SK (1975) Adriamycin — A review. J Natl Cancer Inst 55: 1265–1274
Ganzina F (1983) 4'-epi-doxorubicin, a new analog of doxorubicin: A preliminary overview of preclinical and clinical data. Cancer Treat Rev 10: 1–22
Hurteloup P, Cappelaere P, Armand JP, Mathé G (1983) Phase II clinical evaluation of 4'epi-doxorubicin. Cancer Treat Rep 67: 337–341
Ganzina F, Di Pietro N, Magni O (1985) Clinical toxicity of 4'-epi-doxorubicin (epirubicin). Tumori 71: 233–240
Eksborg S, Ehrsson H (1984) Liquid chromatography in anticancer drug research with special reference to anthraquinone glycosides. J Pharm Biomed Anal 2: 297–303
Gibaldi M, Perrier D (1975) Pharmacokinetics. Marcel Dekker, New York
Lee, Y-T, Chan KK, Harris PA, Cohen JL (1980) Distribution of adriamycin in cancer patients. Tissue uptakes, plasma concentration after i. v. and hepatic i. a. administration. Cancer 45: 2231–2239
Chlebowski RT, Chan KK, Tong MJ, Weiner JM, Ryden VMJ, Bateman JR (1981) Adriamycin and methyl-CCNU combination therapy in hepatocellular carcinoma. Clinical and pharmacokinetic aspects. Cancer 48: 1088–1095
Eksborg S, Strandler H-S, Edsmyr F, Näslund I, Tahvanainen P (1985) Pharmacokinetic study of IV infusions of adriamycin. Eur J Clin Pharmacol 28: 205–212
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
Weenen H, Lankelma J, Penders PGM, McVie JG, Ten Bokkel Huinink WW, de Planque MM, Pinedo HM (1983) Pharmacokinetics of 4'-epi-doxorubicin in man. Invest New Drugs 1: 59–64
Martini A, Moro E, Pacciarini MA, Tamassia V, Natale N, Piazza E (1984) Cross-over study of pharmacokinetics and haematological toxicity of 4'-epi-doxorubicin in cancer patients. Int J Clin Pharm Res 4: 231–238
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 Exptl Clin Res 9: 775–779
Robert J, Vrignaud P, Nguyen-Ngoc T, Illiadis 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
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Eksborg, S., Stendahl, U. & Lönroth, U. Comparative pharmacokinetic study of adriamycin and 4'epi-adriamycin after their simultaneous intravenous administration. Eur J Clin Pharmacol 30, 629–631 (1986). https://doi.org/10.1007/BF00542426
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DOI: https://doi.org/10.1007/BF00542426