• 1

    Jacquet JMBressolle FGaltier M, et al.Doxorubicin and doxorubicinol: intra-and inter-individual variations of pharmacokinetic parameters. Cancer Chemother Pharmacol 1990; 27: 219225.

    • Search Google Scholar
    • Export Citation
  • 2

    Piscitelli SCRodvold KARushing DA, et al.Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer. Clin Pharmacol Ther 1993; 53: 555561.

    • Search Google Scholar
    • Export Citation
  • 3

    Preisler HDGessner TAzarnia N, et al.Relationship between plasma adriamycin levels and the outcome of remission induction therapy for acute nonlymphocytic leukemia. Cancer Chemother Pharmacol 1984; 12: 125130.

    • Search Google Scholar
    • Export Citation
  • 4

    Bielack SSErttmann RKempf-Bielack B, et al.Impact of scheduling on toxicity and clinical efficacy of doxorubicin: what do we know in the mid-nineties? Eur J Cancer 1996;32A:16521660.

    • Search Google Scholar
    • Export Citation
  • 5

    Stallard SMorrison JGGeorge WD, et al.Distribution of doxorubicin to normal breast and tumour tissue in patients under-going mastectomy. Cancer Chemother Pharmacol 1990; 25: 286290.

    • Search Google Scholar
    • Export Citation
  • 6

    Rodvold KARushing DATewksbury DA. Doxorubicin clearance in the obese. J Clin Oncol 1988; 6: 13211327.

  • 7

    Twelves CJDobbs NAGillies HC, et al.Doxorubicin pharmacokinetics: the effect of abnormal liver biochemistry tests. Cancer Chemother Pharmacol 1998; 42: 229234.

    • Search Google Scholar
    • Export Citation
  • 8

    Behnia KBoroujerdi M. Investigation of the enterohepatic recirculation of adriamycin and its metabolites by a linked-rat model. Cancer Chemother Pharmacol 1998; 41: 370376.

    • Search Google Scholar
    • Export Citation
  • 9

    Bronchud MHMargison JMHowell A, et al.Comparative pharmacokinetics of escalating doses of doxorubicin in patients with metastatic breast cancer. Cancer Chemother Pharmacol 1990; 25: 435439.

    • Search Google Scholar
    • Export Citation
  • 10

    Dobbs NATwelves CJGillies H, et al.Gender affects doxorubicin pharmacokinetics in patients with normal liver biochemistry. Cancer Chemother Pharmacol 1995; 36: 473476.

    • Search Google Scholar
    • Export Citation
  • 11

    Cusack BJYoung SPLoseke VL, et al.Effect of a low-protein diet on doxorubicin pharmacokinetics in the rabbit. Cancer Chemother Pharmacol 1992; 30: 145148.

    • Search Google Scholar
    • Export Citation
  • 12

    Maguire PJFettman MJSmith MO, et al.Effects of diet on pharmacokinetics of phenobarbital in healthy dogs. J Am Vet Med Assoc 2000; 217: 847852.

    • Search Google Scholar
    • Export Citation
  • 13

    Ogilvie GKFettman MJMallinckrodt CH, et al.Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and survival time for dogs with lymphoma: a double-blind, randomized placebo-controlled study. Cancer 2000; 88: 19161928.

    • Search Google Scholar
    • Export Citation
  • 14

    Guffy MMNorth JABurns CP. Effect of cellular fatty acid alteration on adriamycin sensitivity in cultured L1210 murine leukemia cells. Cancer Res 1984; 44: 18631866.

    • Search Google Scholar
    • Export Citation
  • 15

    Hagve T-AWoldseth BBrox J, et al.Membrane fluidity and fatty acid metabolism in kidney cells from rats fed purified eicos-apentaenoic acid or purified docosahexaenoic acid. Scand J Clin Lab Invest 1998; 58: 187194.

    • Search Google Scholar
    • Export Citation
  • 16

    Hardman WEAvula CPFernandes G, et al.Three percent dietary fish oil concentrate increased efficacy of doxorubicin against MDA-MB 231 breast cancer xenografts. Clin Cancer Res 2001; 7: 20412049.

    • Search Google Scholar
    • Export Citation
  • 17

    Fettman MJPhillips RW. Dietary effects on drug metabolism. In: Hand MSThatcher CDRemillard RL, et al, eds. Small animal clinical nutrition. 4th ed. Marceline, Mo: Walsworth Publishing Co, 2000; 923939.

    • Search Google Scholar
    • Export Citation
  • 18

    Abulrob ANMason MBryce R, et al.The effect of fatty acids and analogues upon intracellular levels of doxorubicin in cells displaying P-glycoprotein mediated multidrug resistance. J Drug Target 2000; 8: 247256.

    • Search Google Scholar
    • Export Citation
  • 19

    Das UNMadhavi NSravan Kumar G, et al.Can tumour cell drug resistance be reversed by essential fatty acids and their metabolites? Prostaglandins Leukot Essent Fatty Acids 1998; 58: 3954.

    • Search Google Scholar
    • Export Citation
  • 20

    Hansen RAOgilvie GKDavenport DJ, et al.Duration of effects of dietary fish oil supplementation on serum eicosapentaenoic acid and docosahexaenoic acid concentrations in dogs. Am J Vet Res 1998; 59: 864868.

    • Search Google Scholar
    • Export Citation
  • 21

    Valerius KDOgilvie GKMallinckrodt CH, et al.Doxorubicin alone or in combination with asparaginase, followed by cyclophosphamide, vincristine, and prednisone for treatment of multicentric lymphoma in dogs: 121 cases (1987–1995). J Am Vet Med Assoc 1997; 210: 512516.

    • Search Google Scholar
    • Export Citation
  • 22

    de Jong JGeurand WSSchoofs PR, et al.Simple and sensitive quantification of anthracyclines in mouse atrial tissue using high-performance liquid chromatography and fluorescence detection. J Chromatogr 1991; 570: 209216.

    • Search Google Scholar
    • Export Citation
  • 23

    Gustafson DLRastatter JCColombo T, et al.Doxorubicin pharmacokinetics: macromolecule binding, metabolism, and excretion in the context of a physiologic model. J Pharm Sci 2002; 91: 14881501.

    • Search Google Scholar
    • Export Citation
  • 24

    Ratain MJRobert Jvan der Vijgh WJF. Limited sampling models for doxorubicin pharmacokinetics. J Clin Oncol 1991; 9: 871876.

  • 25

    Rousseau AMarquet P. Application of pharmacokinetic modeling to the routine therapeutic drug monitoring of anticancer drugs. Fundam Clin Pharmacol 2002; 16: 253262.

    • Search Google Scholar
    • Export Citation
  • 26

    Arrington KALegendre AMTabeling GS, et al.Comparison of body surface area-based and weight-based dosage protocols for doxorubicin administration in dogs. Am J Vet Res 1994; 55: 15871592.

    • Search Google Scholar
    • Export Citation
  • 27

    Waddle JRFine RLCase BC, et al.Phase I and pharmacokinetic analysis of high-dose tamoxifen and chemotherapy in normal and tumor-bearing dogs. Cancer Chemother Pharmacol 1999; 44: 7480.

    • Search Google Scholar
    • Export Citation
  • 28

    Wilke AVJenkins CMilligan AJ, et al.Effect of hyperthermia on normal tissue toxicity and on adriamycin pharmacokinetics in dogs. Cancer Res 1991; 51: 16801683.

    • Search Google Scholar
    • Export Citation
  • 29

    Tonetti MAstroff ABSatterfield W, et al.Pharmacokinetic properties of doxorubicin encapsulated in glutaraldehyde-treated canine erythrocytes. Am J Vet Res 1991; 52: 16301635.

    • Search Google Scholar
    • Export Citation
  • 30

    Baldwin JRPhillips BAOvermyer SK, et al.Influence of the cardioprotective agent dexrazoxane on doxorubicin pharmacokinetics in the dog. Cancer Chemother Pharmacol 1992; 30: 433438.

    • Search Google Scholar
    • Export Citation
  • 31

    Oosterbaan MJMDirks RJMVree TB, et al.Pharmacokinetics of anthracyclines in dogs: evidence for structure-related body distribution and reduction to their hydroxy metabolites. Pharm Res 1984; 1: 3338.

    • Search Google Scholar
    • Export Citation
  • 32

    Price GSPage RLRiviere JE, et al.Effect of whole-body hyperthermia on lonidamine and doxorubicin pharmacokinetics and toxicity in dogs. Int J Hyperthermia 1995; 11: 545559.

    • Search Google Scholar
    • Export Citation
  • 33

    Ku YKusunoki NKitagawa T, et al.Pharmacokinetics of adriamycin and cisplatin for anhepatic chemotherapy during liver transplantation. Cancer Chemother Pharmacol 1997; 40: 457462.

    • Search Google Scholar
    • Export Citation
  • 34

    Riviere JE. Study design and data analysis. In: Riviere JE, ed. Comparative pharmacokinetics: principles, techniques and applications. Ames, Iowa: Iowa State University Press, 1999; 239259.

    • Search Google Scholar
    • Export Citation
  • 35

    Leca FMarchiset-Leca DNoble A, et al.New data on the pharmacokinetics of adriamycin and its major metabolite, adriamycinol. Eur J Drug Metab Pharmacokinet 1991; 16: 107111.

    • Search Google Scholar
    • Export Citation
  • 36

    Gustafson DLLong MEZirrolli JA, et al.Analysis of docetaxel pharmacokinetics in humans with the inclusion of later sampling time-points afforded by the use of a sensitive tandem LCMS assay. Cancer Chemother Pharmacol 2003; 52: 159166.

    • Search Google Scholar
    • Export Citation
  • 37

    Sturgill MGAugust DABrenner DE. Hepatic enzyme induction with phenobarbital and doxorubicin metabolism and myelotoxicity in the rabbit. Cancer Invest 2000; 18: 197205.

    • Search Google Scholar
    • Export Citation
  • 38

    Hirafuji MMachida THamaue N, et al.Cardiovascular protective effects of n-3 polyunsaturated fatty acids with special emphasis on docosahexaenoic acid. J Pharm Sci 2003; 92: 308316.

    • Search Google Scholar
    • Export Citation
  • 39

    Cognault SJourdan MLGermain E, et al.Effect of an α-linolenic acid-rich diet on rat mammary tumor growth depends on the dietary oxidative status. Nutr Cancer 2000; 36: 3341.

    • Search Google Scholar
    • Export Citation

Evaluation of the effects of dietary n-3 fatty acid supplementation on the pharmacokinetics of doxorubicin in dogs with lymphoma

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  • 1 Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.
  • | 2 Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.
  • | 3 University of Colorado Health Sciences Center, CU Cancer Center Pharmacology Core, 4200 E Ninth Ave, Denver, CO 80262.
  • | 4 University of Colorado Health Sciences Center, CU Cancer Center Pharmacology Core, 4200 E Ninth Ave, Denver, CO 80262.
  • | 5 Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.
  • | 6 Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.
  • | 7 Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.
  • | 8 Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.
  • | 9 Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.
  • | 10 Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

Abstract

Objective—To determine the effect of dietary n-3 fatty acids on the pharmacokinetics of doxorubicin in dogs with lymphoma.

Animals—23 dogs with lymphoma in stages IIIa, IVa, and Va.

Procedure—Dogs receiving doxorubicin chemotherapy were randomly allocated to receive food with a high (test group) or low (control group) content of n-3 fatty acids. Serum doxorubicin and doxorubicinol concentrations were measured via high-performance liquid chromatography before and 6 to 9 weeks after initiation of the diets. Lymph node concentrations of doxorubicin were assessed 6 hours after the initial treatment. Dogs' body composition was assessed by means of dual-energy x-ray absorptiometry scans.

Results—No significant differences in doxorubicin pharmacokinetics were detected between treatment groups. Significant differences existed between the first and second sampling times among all dogs for area under the curve, maximum serum concentration, and clearance. Differences in body composition did not affect measured pharmacokinetic variables. The terminal elimination half-life was longer in dogs in which a long-term remission was achieved than in dogs that did not have remission.

Conclusions and Clinical Relevance—Dietary supplementation of n-3 fatty acids is common in veterinary patients with neoplasia, but supplementation did not affect doxorubicin pharmacokinetics in this population of dogs. Explanations for the beneficial effects of n-3 fatty acids other than alterations in the pharmacokinetics of chemotherapy drugs should be investigated. Dogs may metabolize drugs differently prior to remission of lymphoma than when in remission. The pharmacokinetics of doxorubicin at the time of the first administration may predict response to treatment.

Abstract

Objective—To determine the effect of dietary n-3 fatty acids on the pharmacokinetics of doxorubicin in dogs with lymphoma.

Animals—23 dogs with lymphoma in stages IIIa, IVa, and Va.

Procedure—Dogs receiving doxorubicin chemotherapy were randomly allocated to receive food with a high (test group) or low (control group) content of n-3 fatty acids. Serum doxorubicin and doxorubicinol concentrations were measured via high-performance liquid chromatography before and 6 to 9 weeks after initiation of the diets. Lymph node concentrations of doxorubicin were assessed 6 hours after the initial treatment. Dogs' body composition was assessed by means of dual-energy x-ray absorptiometry scans.

Results—No significant differences in doxorubicin pharmacokinetics were detected between treatment groups. Significant differences existed between the first and second sampling times among all dogs for area under the curve, maximum serum concentration, and clearance. Differences in body composition did not affect measured pharmacokinetic variables. The terminal elimination half-life was longer in dogs in which a long-term remission was achieved than in dogs that did not have remission.

Conclusions and Clinical Relevance—Dietary supplementation of n-3 fatty acids is common in veterinary patients with neoplasia, but supplementation did not affect doxorubicin pharmacokinetics in this population of dogs. Explanations for the beneficial effects of n-3 fatty acids other than alterations in the pharmacokinetics of chemotherapy drugs should be investigated. Dogs may metabolize drugs differently prior to remission of lymphoma than when in remission. The pharmacokinetics of doxorubicin at the time of the first administration may predict response to treatment.

Contributor Notes

Address correspondence to Dr. Selting.

Dr. Selting's present address is Veterinary Medical Teaching Hospital, College of Veterinary Medicine, Columbia, MO 65211.

Dr. Ogilvie's present address is CVS Angel Care Cancer Center, 100 N Rancho Santa Fe, San Marcos, CA 92069.

Dr. Hansen's present address is Department of Health Promotion and Human Performance, Weber State University, Ogden, UT 84408-2801.

Supported by the Shipley Grant.

The authors thank Dr. Susan Plaza and Juanita Kenney for technical assistance.