Summary
The chronopharmacokinetics of doxorubicin (DOX) has been studied in 18 patients suffering from breast cancer. They received combined chemotherapy, including DOX (50 mg/m2 as an iv bolus), given at two different times (09.00 h or 21.00 h). The two randomized courses of the protocol were given to each patient at a four week interval.
The total body clearance (CL) of DOX was significantly decreased when the drug was administered at 21.00 h, resulting in a longer elimination half-life and an increase in AUC. The renal clearance of DOX did not differ at the different times of administration, and it appears that the decrease in CL was related to a change in hepatic blood flow. The volume of distribution of the drug was not changed.
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References
Aymard N, Soulairac A (1979) Chronobiological changes in pharmacokinetics of dipotassic clorazepate, a benzodiazepine: In: Reinberg A, Halberg J (eds) Chronopharmacology. Pergamon, Oxford, pp 111–116
Bachur NR, Steele M, Meriwether ND et al. (1976) Cellular pharmacodynamics of several anthracycline antibiotics. J Med Chem 19: 651–654
Ballet F, Vrignaud P, Robert J, Rey C, Poupon R (1987) Hepatic extraction, metabolism and biliary excretion of doxorubicin in the isolated prefused rat liver. Cancer Chemother Pharmacol 19: 240–245
Celio LA, DiGregorio GJ, Ruch E et al. (1983) Doxorubicin and 5 fluoro-uracil plasma concentrations and detectability in parotid saliva. Eur J Clin Pharmacol 24: 261–266
Clench J, Reinberg A, Dziewanowska Z, Ghata J, Dupont J (1981) Circadian changes in the bioavailability and effects of indomethacin in healthy subjects. Eur J Clin Pharmacol 20: 359–369
Garnick MB, Ensminger WD, Israel M (1979) A clinical-pharmacological evaluation of hepatic arterial infusion of adriamycin. Cancer Res 39: 4105–4110
Gil P, Favre R, Durand A, Iliadis A, Cano JP, Carcassonne Y (1983) Time dependency of adriamycin and adriamycinol kinetics. Cancer Chemother Pharmacol 10: 120–124
Greene RF, Collins JM, Jenkins JF (1983) Plasma pharmacokinetics of adriamycin and adriamycinol. Implications for the design of in vitro experiments and treatment protocols. Cancer Res 43: 3417–3421
Hrushesky W, Levi F, Kennedy BJ (1980) Cis-diammine-dichloroplatinum (DDP) toxicity to the kidney reduced by circadian timing. Proc Am Soc Clin Oncol 21: C45 (abstract)
Hrushesky WJM (1985) Circadian timing of cancer therapy. Science 228: 73–75
Hrushesky WJM, Von Roemeling R, Sothern RB (1989) Circadian chronotherapy: from animal experiments to human cancer chemotherapy. In: Lemmer B (ed) Chronopharmacology, cellular and biochemical interactions. Dekker, New York, pp 439–473
Labrecque G, Belanger PM, Dore F, Lalande M (1988) 24 hour variations in the distribution of labeled microspheres to the intestin, liver and kidneys. Ann Rev Chronopharmacol 5: 445–448
Levi F (1987) Chronopharmacology of anticancer agents and cancer chronotherapy in Clinical Pharmacology, Kummerle EB (ed) Chapter II-2.15.3.3, pp 1–17
Mormont C, Boughattas N, Levi F (1989) Mechanisms of circadian rhythms in the toxicity and efficacy of anticancer drugs: relevance for the development of new analogs. In: Lemmer B (ed) Chronopharmacology, cellular and biochemical interactions. Dekker, New York, pp 395–437
Petit E, Milano G, Levi F, Thyss A, Bailleul F, Schneider M (1988) Circadian rhythm-varying plasma concentration of 5-fluorouracil during a five-day continuous venous infusion at a constant rate in cancer patients. Cancer Res 48: 1676–1679
Piazza E, Donelli MG, Broggini M, Sessa C, Natale N, Ottolengli Marsoni S, Libretti A, Manzioni C, Morasca L (1980) Earlyphase pharmacokinetics of doxorubicin (adriamycin) in plasma of cancer patients during single and multiple drug therapy. Cancer Treat Rep 64: 845–854
Radzialowski FW, Bousquet WF (1968) Daily rhythm variation in hepatic drug metabolism in the rat and the mouse. J Pharmacol Exp Ther 163: 229–238
Reinberg A, Smolensky MH (1982) Circadian changes of drug disposition in man. Clin Pharmacokinet 7: 401–420
Robert J, Illiadis A, Hoerni B, Cano JP, Durand M, Lagarde C (1982) Pharmacokinetics of adriamycin in patients with breast cancer: correlation between pharmacokinetics parameters and clinical short-term response. Eur J Cancer Clin Oncol 18: 739–745
Robert J, Hoerni B, Vrignaud P, Lagarde C (1983) Early-phase pharmacokinetics of doxorubicin in non-Hodgkin lymphoma patients. Dose-dependent and time-dependent pharmacokinetic parameters. Cancer Chemother Pharmacol 10: 115–119
Robert J, Vrignaud P, N'Guyen-Ndoc 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
Rowland M, Tozer T (1980) Clinical pharmacokinetics: concepts and applications. Lea and Febiger, Philadelphia
Shively CA, Simons RJ, Passananti GT, Dvorchik BH, Vessel ES (1981) Dietary patterns and diurnal variations in aminopyrine disposition. Clin Pharmacol Ther 29: 65–73
Speth PAJ, Van Hoesel QCCM, Haanen C (1988) Clinical pharmacokinetics of doxorubicin. Clin Pharmacokinet 15: 15–31
Sqalli A, Labat C, Oustrin J, Houin G, Coulais Y, Bugat R, Carton M (1989) Rapid quantitative determination of doxorubicin and its metabolites in biological samples. Ann Biol Clin 47: 63–66
Takanashi S, Bachur NR (1976) Adriamycin metabolism in man, evidence for urinary metabolites. Drug Metab Disp 4: 79–87
Touitou Y, Touitou C, Bogdan A, Beck H, Reinberg A (1979) Circadian rhythms in serum total proteins observed differences according to age and mental health. Chronobiologia 6: 164
Wilkinson GR (1987) Clearance approaches in pharmacology. Pharmacol Rev 39: 1–47
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Canal, P., Sqalli, A., de Forni, M. et al. Chronopharmacokinetics of doxorubicin in patients with breast cancer. Eur J Clin Pharmacol 40, 287–291 (1991). https://doi.org/10.1007/BF00315211
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DOI: https://doi.org/10.1007/BF00315211