Skip to main content
SpringerLink
Log in

Effects of Food on the Clinical Pharmacokinetics of Anticancer Agents

Underlying Mechanisms and Implications for Oral Chemotherapy

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Pharmacokinetic interactions between food and orally administered drugs involve changes mainly in the absorption and metabolism of a drug, and may have clinical implications. Such interactions, in particular, may be of major clinical significance for cancer chemotherapy since the majority of anticancer agents are toxic, have a low therapeutic index and are administered long term, most often in combination with other cytotoxic agents. The purpose of this review is to compare the pharmacokinetic profiles of various anticancer drugs, including chemopreventive agents that have been examined previously in fasted and fed conditions, and to discuss the underlying basis/mechanisms of food effect in light of a drug’s physicochemical and pharmacokinetic properties. Clinical pharmacokinetic parameters such as maximum concentration, area under the concentration-time curve, time to maximum concentration and half-life for each drug are compared in fasted and fed states, and specific dietary recommendations are summarised accordingly. In addition, the effects of food on the metabolite kinetics and pharmacodynamic responses, and the potential role of food effect in the modulation of oral biovariability and multidrug resistance have been extensively discussed. Overall, this comprehensive pharmacokinetic analysis indicates that a broad spectrum of food effects is seen among anticancer agents because of diverse factors regulating each drug’s oral bioavailability and its interactions with food. The consideration of such effects is important, as it could lead to more rational pharmacological monitoring and possibly improve the oral chemotherapy of cancer in children, adults and the elderly.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV
Table V
Table VI
Table VII
Table VIII

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Greco FA. Evolving role of oral chemotherapy for the treatment of patients with neoplasms. Oncology 1998; 12 (3 Suppl. 4): 43–50

    PubMed  CAS  Google Scholar 

  2. DeMario MD, Ratain MJ. Oral chemotherapy: rationale and future directions. J Clin Oncol 1998; 16: 2557–67

    PubMed  CAS  Google Scholar 

  3. Bardelmeijer HA, van Tellingen O, Schellens JH, et al. The oral route for the administration of cytotoxic drugs: strategies to increase the efficiency and consistency of drug delivery. Invest New Drugs 2000; 18: 231–41

    PubMed  CAS  Google Scholar 

  4. Liu G, Franssen E, Fitch MI, et al. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 1997; 15: 110–5

    PubMed  CAS  Google Scholar 

  5. Gerrits CJ, de Jonge MJ, Schellens JH, et al. Topoisomerase I inhibitors: the relevance of prolonged exposure for present clinical development. Br J Cancer 1997; 76: 952–62

    PubMed  CAS  Google Scholar 

  6. Moore MJ, Theissen JJ. Cytotoxics and irreversible effects. In: van Boxtel CJ, Holford NHG, Danhof M, editors. The in vivo study of drug action: principles and applications of kinetic-dynamic modeling. Amsterdam: Elsevier, 1992: 377–400

    Google Scholar 

  7. Lee CR, Nicholson PW, Souhami RL, et al. Patient compliance with oral chemotherapy as assessed by a novel electronic technique. J Clin Oncol 1992; 10: 1007–13

    PubMed  CAS  Google Scholar 

  8. Singh BN. Effects of food on clinical pharmacokinetics. Clin Pharmacokinet 1999; 37: 213–55

    PubMed  CAS  Google Scholar 

  9. Fleisher D, Li C, Zhou Y, et al. Drug, meal and formulation interactions influencing drug absorption after oral administration. Clinical implications. Clin Pharmacokinet 1999; 36: 233–54

    PubMed  CAS  Google Scholar 

  10. Welling PG. Effects of food on drug absorption. Annu Rev Nutr 1996; 16: 383–415

    PubMed  CAS  Google Scholar 

  11. Brandt JL, Castleman L, Ruskin HD, et al. The effects of oral protein and glucose feeding on splanchnic blood flow and oxygen utilization in normal and cirrhotic subjects. J Clin Invest 1955; 34: 1017–25

    PubMed  CAS  Google Scholar 

  12. al-Behaisi S, Antal I, Morovjan G, et al. Study of the acid buffering capacity of dietary components regarding food-drug interactions [in Hungarian]. Acta Pharm Hung 2002; 72: 185–90

    PubMed  CAS  Google Scholar 

  13. Center for Drug Evaluation and Research, Food and Drug Administration. Guidance for industry: food-effect bioavailability and fed bioequivalence studies. Rockville (MD): Food and Drug Administration, 2002 Dec

    Google Scholar 

  14. Ehrsson H, Wallin I, Simonsson B, et al. Effect of food on pharmacokinetics of chlorambucil and its main metabolite, phenylacetic acid mustard. Eur J Clin Pharmacol 1984; 27: 111–4

    PubMed  CAS  Google Scholar 

  15. Schuler U, Schroer S, Kuhnle A, et al. Busulfan pharmacokinetics in bone marrow transplant patients: is drug monitoring warranted? Bone Marrow Transplant 1994; 14: 759–65

    PubMed  CAS  Google Scholar 

  16. Reece PA, Kotasek D, Morris RG, et al. The effect of food on oral melphalan absorption. Cancer Chemother Pharmacol 1986; 16: 194–7

    PubMed  CAS  Google Scholar 

  17. Bosanquet AG, Gilby ED. Comparison of the fed and fasting states on the absorption of melphalan in multiple myeloma. Cancer Chemother Pharmacol 1984; 12: 183–6

    PubMed  CAS  Google Scholar 

  18. Barker IK, Crawford SM, Fell AF. Determination of altretamine in human plasma with high-performance liquid chromatography. J Chromatogr B Biomed Appl 1994; 660: 121–6

    PubMed  CAS  Google Scholar 

  19. Gunnarsson PO, Davidsson T, Andersson SB, et al. Impairment of estramustine phosphate absorption by concurrent intake of milk and food. Eur J Clin Pharmacol 1990; 38: 189–93

    PubMed  CAS  Google Scholar 

  20. Adair CG, Bridges JM, Desai ZR. Can food affect the bioavailability of chlorambucil in patients with haematological malignancies? Cancer Chemother Pharmacol 1986; 17: 99–102

    PubMed  CAS  Google Scholar 

  21. Brada M, Judson I, Beale P, et al. Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies. Br J Cancer 1999; 81: 1022–30

    PubMed  CAS  Google Scholar 

  22. Sioufi A, Sandrenan N, Godbillon J, et al. Comparative bioavailability of letrozole under fed and fasting conditions in 12 healthy subjects after a 2.5mg single oral administration. Biopharm Drug Dispos 1997; 18: 489–97

    PubMed  CAS  Google Scholar 

  23. Choi RL, Sun JX, Kochak GM. The effect of food on the relative bioavailability of fadrozole hydrochloride. Biopharm Drug Dispos 1993; 14: 779–84

    PubMed  CAS  Google Scholar 

  24. Flomax® (tamsulosin hydrochloride) capsules prescribing information. Ridgefield (CT); Boehringer Ingelheim Pharmaceuticals, Inc., 1998

  25. Katashima M, Irino T, Shimojo F, et al. Pharmacokinetics and pharmacodynamics of FK143, a nonsteroidal inhibitor of steroid 5α-reductase, in healthy volunteers. Clin Pharmacol Ther 1998; 63: 354–66

    PubMed  CAS  Google Scholar 

  26. Charman WN, Rogge MC, Boddy AW, et al. Effect of food and a monoglyceride emulsion formulation on danazol bioavailability. J Clin Pharmacol 1993; 33: 381–6

    PubMed  CAS  Google Scholar 

  27. Poggesi I, Jannuzzo MG, Di Salle E, et al. Effect of food and formulation on the pharmacokinetics (PK) and pharmacodynamics (PD) of a single oral dose of exemestane (Aromasin®, EXE) [abstract]. 35th Annual Meeting of the American Society of Clinical Oncology; 1999 May 15–18; Atlanta, A741

    Google Scholar 

  28. Cockshott ID, Oliver SD, Young JJ, et al. The effect of food on the pharmacokinetics of the bicalutamide (’Casodex’) enantiomers. Biopharm Drug Dispos 1997; 18: 499–507

    PubMed  CAS  Google Scholar 

  29. Ohtawa M, Morikawa H, Shimazaki J. Pharmacokinetics and biochemical efficacy after single and multiple oral administration of N-(2-methyl-2-propyl)-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide, a new type of specific competitive inhibitor of testosterone 5α-reductase, in volunteers. Eur J Drug Metab Pharmacokinet 1991; 16: 15–21

    PubMed  CAS  Google Scholar 

  30. Nomura Y, Abe O, Enomoto K, et al. Phase I study of TAT-59 (a new antiestrogen) in breast cancer. TAT-59 study group [in Japanese]. Gan To Kagaku Ryoho 1998; 25: 553–61

    PubMed  CAS  Google Scholar 

  31. Miura S, Tominaga T, Koyama H, et al. Phase I single-dose administration study of exemestane in postmenopausal women [in Japanese]. Gan To Kagaku Ryoho 2002; 29: 1179–87

    PubMed  Google Scholar 

  32. Janisch L, Mani S, Schilsky RL, et al. Phase I study to determine the effects of food on the absorption of oral 776C85 (776) plus 5-fluorouracil (FU) in patients (pts) with advanced cancer [abstract]. 34th Annual Meeting of the American Society of Clinical Oncology; 1998 May 16–19; Los Angeles, A862

    Google Scholar 

  33. Hamilton RA, Kremer JM. The effects of food on methotrexate absorption. J Rheumatol 1995; 22: 630–2

    PubMed  CAS  Google Scholar 

  34. Madanat F, Awidi A, Shaheen O, et al. Effects of food and gender on the pharmacokinetics of methotrexate in children. Res Commun Chem Pathol Pharmacol 1987; 55: 279–82

    PubMed  CAS  Google Scholar 

  35. Albertioni F, Juliusson G, Liliemark J. On the bioavailability of 2-chloro-2′-deoxyadenosine (CdA): the influence of food and omeprazole. Eur J Clin Pharmacol 1993; 44: 579–82

    PubMed  CAS  Google Scholar 

  36. Hughes AN, Rafi I, Griffin MJ, et al. Phase I studies with the nonclassical antifolate nolatrexed dihydrochloride (AG337, THYMITAQ) administered orally for 5 days. Clin Cancer Res 1999; 5: 111–8

    PubMed  CAS  Google Scholar 

  37. Riccardi R, Balis FM, Ferrara P, et al. Influence of food intake on bioavailability of oral 6-mercaptopurine in children with acute lymphoblastic leukemia. Pediatr Hematol Oncol 1986; 3: 319–24

    PubMed  CAS  Google Scholar 

  38. Riccardi R, Lasorella A, Mastrangelo R. Factors affecting the clinical pharmacology of antileukemic drugs. Dev Oncol 1987; 44: 179–84

    Google Scholar 

  39. Burton NK, Barnett MJ, Aherne GW, et al. The effect of food on the oral administration of 6-mercaptopurine. Cancer Chemother Pharmacol 1986; 18: 90–1

    PubMed  CAS  Google Scholar 

  40. Rivard GE, Lin KT, Leclerc JM, et al. Milk could decrease the bioavailability of 6-mercaptopurine. Am J Pediatr Hematol Oncol 1989; 11: 402–6

    PubMed  CAS  Google Scholar 

  41. Pinkerton CR, Welshman SG, Glasgow JF, et al. Can food influence the absorption of methotrexate in children with acute lymphoblastic leukaemia? Lancet 1980; II: 944–6

    Google Scholar 

  42. Reigner B, Verweij J, Dirix L, et al. Effect of food on the pharmacokinetics of capecitabine and its metabolites following oral administration in cancer patients. Clin Cancer Res 1998; 4: 941–8

    PubMed  CAS  Google Scholar 

  43. Lancaster DL, Patel N, Lennard L, et al. 6-Thioguanine in children with acute lymphoblastic leukaemia: influence of food on parent drug pharmacokinetics and 6-thioguanine nucleotide concentrations. Br J Clin Pharmacol 2001; 51: 531–9

    PubMed  CAS  Google Scholar 

  44. Damle B, Ravandi F, Kaul S, et al. Effect of food on the oral bioavailability of UFT and leucovorin in cancer patients. Clin Cancer Res 2001; 7: 517–23

    PubMed  CAS  Google Scholar 

  45. Lafolie P, Bjork O, Hayder S, et al. Variability of 6-mercaptopurine pharmacokinetics during oral maintenance therapy of children with acute leukemia. Med Oncol Tumor Pharmacother 1989; 6: 259–65

    PubMed  CAS  Google Scholar 

  46. Lönnerholm G, Kreuger A, Lindström B, et al. Oral mercaptopurine in childhood leukemia: influence of food intake on bioavailability. Pediatr Hematol Oncol 1989; 6: 105–12

    PubMed  Google Scholar 

  47. Oscier D, Orchard JA, Culligan D, et al. The bioavailability of oral fludarabine phosphate is unaffected by food. Hematol J 2001; 2: 316–21

    PubMed  CAS  Google Scholar 

  48. Rowinsky EK, Lucas VS, Hsieh AL, et al. The effects of food and divided dosing on the bioavailability of oral vinorelbine. Cancer Chemother Pharmacol 1996; 39: 9–16

    PubMed  CAS  Google Scholar 

  49. Variol P, Roche H, Fumoleau P, et al. Effects of food study on pharmacokinetic (PK) profile and safety of oral vinorelbine (VRL) in patients (pts) with solid tumors or lymphomas [abstract]. 34th Annual Meeting of the American Society of Clinical Oncology; 1998 May 16–19; Los Angeles, A849

    Google Scholar 

  50. Ripple GH, Gould MN, Arzoomanian RZ, et al. Phase I clinical and pharmacokinetic study of perillyl alcohol administered four times a day. Clin Cancer Res 2000; 6: 390–6

    PubMed  CAS  Google Scholar 

  51. McNamara PJ, Jewell RC, Jensen BK, et al. Food increases the bioavailability of acitretin. J Clin Pharmacol 1988; 28: 1051–5

    PubMed  CAS  Google Scholar 

  52. Colburn WA, Gibson DM, Rodriguez LC, et al. Effect of meals on the kinetics of etretinate. J Clin Pharmacol 1985; 25: 583–9

    PubMed  CAS  Google Scholar 

  53. DiGiovanna JJ, Gross EG, McClean SW, et al. Etretinate: effect of milk intake on absorption. J Invest Dermatol 1984; 82: 636–40

    PubMed  CAS  Google Scholar 

  54. Colburn WA, Gibson DM, Wiens RE, et al. Food increases the bioavailability of isotretinoin. J Clin Pharmacol 1983; 23: 534–9

    PubMed  CAS  Google Scholar 

  55. Usuki K, Endo M, Osawa M, et al. Pharmacokinetics of all-trans-retinoic acid in Japanese patients with acute promyelocytic leukemia. Int J Hematol 1996; 63: 19–23

    PubMed  CAS  Google Scholar 

  56. Doose DR, Minn FL, Stellar S, et al. Effects of meals and meal composition on the bioavailability of fenretinide. J Clin Pharmacol 1992; 32: 1089–95

    PubMed  CAS  Google Scholar 

  57. Holazo AA, Pinili EE, De Grazia FT, et al. Influence of food on the bioavailability of Ro 15-0778 in humans. Pharm Res 1990; 7: 777–9

    PubMed  CAS  Google Scholar 

  58. Herben VMM, Rosing H, Ten Bokkel Huinink WW, et al. Oral topotecan: bioavailability and effect of food co-administration. Br J Cancer 1999; 80: 1380–6

    PubMed  Google Scholar 

  59. Paxton JW. The effect of food on the bioavailability and kinetics of the anticancer drug amsacrine and a new analogue, N-5-dimethyl-9-[ (2-methoxy-4-methylsulphonylamino) phenylamino]4 acridinecarboxamide in rabbits. J Pharm Pharmacol 1986; 38: 837–40

    PubMed  CAS  Google Scholar 

  60. Schöffski P, Herr A, Vermorken JB, et al. Clinical phase II study and pharmacological evaluation of rubitecan in non-pretreated patients with metastatic colorectal cancer: significant effect of food intake on the bioavailability of the oral camptothecin analogue. Eur J Cancer 2002; 38: 807–13

    PubMed  Google Scholar 

  61. Eksborg S, Söderberg M, Nilsson B, et al. Plasma pharmacokinetics of idarubicin and its 13-hydroxymetabolite after intravenous and oral administration under fasting and non-fasting conditions. Acta Oncol 1990; 29: 921–5

    PubMed  CAS  Google Scholar 

  62. Gerrits CJ, Schellens JH, Creemers GJ, et al. The bioavailability of oral GI147211 (GG211), a new topoisomerase I inhibitor. Br J Cancer 1997; 76: 946–51

    PubMed  CAS  Google Scholar 

  63. Soepenberg O, Dumez H, Verweiz J, et al. Phase I and pharmacokinetic study of oral irinotecan (CPT-11) on a daily-times 5 schedule every 3 weeks in combination with evaluation of food effect [letter]. Eur J Cancer 2002; 38 Suppl. 7: S46

    Google Scholar 

  64. Harvey VJ, Slevin ML, Joel SP, et al. The effect of food and concurrent chemotherapy on the bioavailability of oral etoposide. Br J Cancer 1985; 52: 363–7

    PubMed  CAS  Google Scholar 

  65. Eskens FA, Levitt NC, Sparreboom A, et al. Effect of food on the pharmacokinetics of oral MMI270B (CGS 27023A), a novel matrix metalloproteinase inhibitor. Clin Cancer Res 2000; 6: 431–3

    PubMed  CAS  Google Scholar 

  66. Rinehart JJ, Wilding G, Willson J, et al. A phase I clinical and pharmacokinetic (PK)/food effect study of oral CI-1033, a pan-erb B tyrosine kinase inhibitor, in patients with advanced solid tumors [abstract]. 39th Annual Meeting of the American Society of Clinical Oncology; 2003 May 31–Jun 3; Chicago, A821

    Google Scholar 

  67. Rowinsky EK, Garrison M, Lorusso P, et al. Administration of CI-1033, an irreversible pan-erb B tyrosine kinase (TK) inhibitor is feasible on a 7-day-on/7-day-off schedule: a phase I, pharmacokinetic (PK), and food effect study [abstract]. 39th Annual Meeting of the American Society of Clinical Oncology; 2003 May 31–Jun 3; Chicago, A807

    Google Scholar 

  68. Koudriakova TB, Zhu XJ, O’Connor P, et al. AG 3433 is a new orally available and metabolically stable MMP inhibitor [abstract]. 90th Annual Meeting of the American Association for Cancer Research; 1999 Apr 10–14; Philadelphia, 3430

    Google Scholar 

  69. Swaisland H, Laight A, Stafford L, et al. Pharmacokinetics and tolerability of the orally active selective epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in healthy volunteers. Clin Pharmacokinet 2001; 40: 297–306

    PubMed  CAS  Google Scholar 

  70. Zhu Y, Statkevich P, Cutler DL, et al. Effect of food on the pharmacokinetics of lonafarnib, a farnesyl protein transferase inhibitor [abstract]. Clin Pharmacol Ther 2002; 71: P82

    Google Scholar 

  71. Bauer KS, Kohn EC, Lush RM, et al. Pharmacokinetics and relative bioavailability of carboxyamido-triazole with respect to food and time of administration: use of a single model for simultaneous determination of changing parameters. J Pharmacokinet Biopharm 1998; 26: 673–87

    PubMed  CAS  Google Scholar 

  72. Berlin J, Tutsch KD, Arzoomanian RZ, et al. Phase I and pharmacokinetic study of a micronized formulation of carboxyamidotriazole, a calcium signal transduction inhibitor: toxicity, bioavailability and the effect of food. Clin Cancer Res 2002; 8: 86–94

    PubMed  CAS  Google Scholar 

  73. Mitchell DY, Reid JM, Parchment RE, et al. Pharmacokinetics (PK) and pharmacodynamics (PD) of the oral MEK inhibitor, CI-1040, following multiple dose administration to patients with advanced cancer [abstract]. 38th Annual Meeting of the American Society of Clinical Oncology; 2002 May 18–21; Orlando, 320

    Google Scholar 

  74. Chien D-S, Daly D, Brubaker WF. Pharmacokinetics of BAY 12-9566 in guinea pigs following intravenous and oral administration [abstract]. 90th Annual Meeting of the American Association for Cancer Research; 1999 Apr 10–14; Philadelphia, 2586

    Google Scholar 

  75. Reckmann AH, Fischer T, Peng B, et al. Effect of food on STI571 GLivec pharmacokinetics and bioavailability [abstract]. 37th Annual Meeting of the American Society of Clinical Oncology; 2001 May 12–15; San Francisco, A1223

    Google Scholar 

  76. Emori H, Yamamoto K, Yokohama S, et al. Bioavailability of bropirimine 250mg tablet in dogs: effect of food. J Pharm Pharmacol 1995; 47: 822–6

    PubMed  CAS  Google Scholar 

  77. Schaaf LJ, Vogelzang NJ, Chambers JH, et al. Effect of food and comparative bioavailability of orally administered bropirimine in solid tumor patients. 31st Annual Meeting of the American Society of Clinical Oncology; 1995 May 20–23; Los Angeles, A1223

    Google Scholar 

  78. Newman MJ, Rodarte JC, Romano SJ, et al. Preclinical characterization and clinical safety/pharmacokinetics of OC144-093, a novel inhibitor of P-glycoprotein-mediated multidrug resistance [abstract]. Clin Cancer Res 1999; 5 Suppl.: A0731

    Google Scholar 

  79. Kondo N, Iwao T, Kikuchi M, et al. Pharmacokinetics of a micronized, poorly water-soluble drug, HO-221, in experimental animals. Biol Pharm Bull 1993; 16: 796–800

    PubMed  CAS  Google Scholar 

  80. Soria I, Myhre P, Horton V, et al. Effect of food on the pharmacokinetics and bioavailability of oral imiquimod relative to a subcutaneous dose. Int J Clin Pharmacol Ther 2000; 38: 476–81

    PubMed  CAS  Google Scholar 

  81. Teo SK, Scheffler MR, Kook KA, et al. Effect of a high-fat meal on thalidomide pharmacokinetics and the relative bioavailability of oral formulations in healthy men and women. Biopharm Drug Dispos 2000; 21: 33–40

    PubMed  CAS  Google Scholar 

  82. Teo SK, Oliver S, Harden J, et al. A phase I, single-blind, placebo-controlled, ascending single oral dose, safety, tolerability and pharmacokinetic study of CDC-501, a novel immunomodulatory-oncologic agent, in healthy male subjects with a comparison of fed and fasted [abstract]. Clin Pharmacol Ther 2002; 71: P93

    Google Scholar 

  83. Prakash S, Foster BJ, Meyer M, et al. Chronic oral administration of CI-994: a phase 1 study. Invest New Drugs 2001; 19: 1–11

    PubMed  CAS  Google Scholar 

  84. Matsushima H, Kamimura H, Soeishi Y, et al. Pharmacokinetics and plasma protein binding of tamsulosin hydrochloride in rats, dogs, and humans. Drug Metab Dispos 1998; 26: 240–5

    PubMed  CAS  Google Scholar 

  85. Melander A, McLean A. Influence of food intake on presystemic clearance of drugs. Clin Pharmacokinet 1983; 8: 286–96

    PubMed  CAS  Google Scholar 

  86. Slevin ML, Clark PI, Joel SP, et al. A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer. J Clin Oncol 1989; 7: 1333–40

    PubMed  CAS  Google Scholar 

  87. Walter-Sack I, Haefeli WE. Consideration of drug absorption in customizing drug therapy [in German]. Ther Umsch 2000; 57: 557–62

    PubMed  CAS  Google Scholar 

  88. Fleisher D, Stevenson C. Fed-State elevation of drug plasma levels inhibited by CCK antagonist [abstract]. Pharm Res 1996; 13 Suppl.: S414

    Google Scholar 

  89. Harris MS, Kennedy JG, Siegesmund KA, et al. Relationship between distention and absorption in rat intestine. I: effect of luminal volume on the morphology of the absorbing surface. Gastroenterology 1988; 94: 1164–71

    PubMed  CAS  Google Scholar 

  90. Harris MS, Kennedy JG. Relationship between distention and absorption in rat intestine. II: effects of volume and flow rate on transport. Gastroenterology 1988; 94: 1172–9

    PubMed  CAS  Google Scholar 

  91. Hamaguchi T, Shinkuma D, Yamanaka Y, et al. Factors affecting dissolution rate of sulpiride from tablets coated with polyvinylacetal diethylaminoacetate, a gastric-fluid-soluble polymer. I: effect of ionic strength of gastrointestinal fluids. Chem Pharm Bull 1995; 43: 1204–11

    CAS  Google Scholar 

  92. Drengler RL, Kuhn JG, Schaaf LJ, et al. Phase I and pharmacokinetic trial of oral irinotecan administered daily for 5 days every 3 weeks in patients with solid tumors. J Clin Oncol 1999; 17: 685–96

    PubMed  CAS  Google Scholar 

  93. Hathcock JN. Metabolic mechanisms of drug-nutrient interactions. Fed Proc 1985; 44: 124–9

    PubMed  CAS  Google Scholar 

  94. Stewart CF, Arbuck SG, Fleming RA, et al. Relation of systemic exposure to unbound etoposide and hematologic toxicity. Clin Pharmacol Ther 1991; 50: 385–93

    PubMed  CAS  Google Scholar 

  95. Jackson PR, Tucker GT, Woods HF. Altered plasma drug binding in cancer: role of alpha 1-acid glycoprotein and albumin. Clin Pharmacol Ther 1982; 32: 295–302

    PubMed  CAS  Google Scholar 

  96. Shargel L, Yu ABC, editors. Applied biopharmaceutics and pharmacokinetics. 3rd ed. Stamford (CT): Appleton & Lange, 1993: 93

    Google Scholar 

  97. Sadzuka Y, Mochizuki E, Iwazaki A, et al. Caffeine enhances adriamycin antitumor activity in Ehrlich ascites carcinoma-bearing mice. Biol Pharm Bull 1995; 18: 159–61

    PubMed  CAS  Google Scholar 

  98. Shao Y, Pardini L, Pardini RS. Enhancement of the antineoplastic effect of mitomycin C by dietary fat. Cancer Res 1994; 54: 6452–7

    PubMed  CAS  Google Scholar 

  99. Reece PA, Dale BM, Morris RG, et al. Effect of L-leucine on oral melphalan kinetics in patients. Cancer Chemother Pharmacol 1987; 20: 256–8

    PubMed  CAS  Google Scholar 

  100. Adair CG, McElnay JC. The effect of dietary amino acids on the gastrointestinal absorption of melphalan and chlorambucil. Cancer Chemother Pharmacol 1987; 19: 343–6

    PubMed  CAS  Google Scholar 

  101. Katsura T, Inui K. Intestinal absorption of drugs mediated by drug transporters: mechanisms and regulation. Drug Metab Pharmacokinet 2003; 18: 1–15

    PubMed  CAS  Google Scholar 

  102. Charman WN, Rogge MC, Boddy AW, et al. Absorption of danazol after administration to different sites of the gastrointestinal tract and the relationship to single- and double-peak phenomena in the plasma profiles. J Clin Pharmacol 1993; 33: 1207–13

    PubMed  CAS  Google Scholar 

  103. Kochak GM, Choi RL, Entwistle EA. Dose proportionality and population characteristics of oral fadrozole hydrochloride, an aromatase inhibitor, in postmenopausal women. Pharm Res 1993; 10: 1760–4

    PubMed  CAS  Google Scholar 

  104. Sioufi A, Gauducheau N, Pineau V, et al. Absolute bioavailability of letrozole in healthy postmenopausal women. Biopharm Drug Dispos 1997; 18: 779–89

    PubMed  CAS  Google Scholar 

  105. Rodriguez GI, Kuhn JG, Weiss GR, et al. A bioavailability and pharmacokinetic study of oral and intravenous hydroxyurea. Blood 1998; 91: 1533–41

    PubMed  CAS  Google Scholar 

  106. Hilger RA, Jacek G, Oberhoff C, et al. Investigation of bioavailability and pharmacokinetics of treosulfan capsules in patients with relapsed ovarian cancer. Cancer Chemother Pharmacol 2000; 45: 483–8

    PubMed  CAS  Google Scholar 

  107. Sietsema WK. The absolute oral bioavailability of selected drugs. Int J Clin Pharmacol Ther Toxicol 1989; 27: 179–211

    PubMed  CAS  Google Scholar 

  108. Damia G, D’Incalci M. Clinical pharmacokinetics of altretamine. Clin Pharmacokinet 1995; 28: 439–48

    PubMed  CAS  Google Scholar 

  109. Strauss JS, Leyden JJ, Lucky AW, et al. Safety of a new micronized formulation of isotretinoin in patients with severe recalcitrant nodular acne: a randomized trial comparing micronized isotretinoin with standard isotretinoin. J Am Acad Dermatol 2001; 45: 196–207

    PubMed  CAS  Google Scholar 

  110. Chen ML, Jackson AJ. The role of metabolites in bioequivalency assessment: II. drugs with linear pharmacokinetics and first-pass effect. Pharm Res 1995; 12: 700–8

    PubMed  CAS  Google Scholar 

  111. Marzo A. Open questions on bioequivalence: some problems and some solutions. Pharmacol Res 1999; 40: 357–68

    PubMed  CAS  Google Scholar 

  112. Sandborn WJ. Azathioprine: state of the art in inflammatory bowel disease. Scand J Gastroenterol 1998; 33 Suppl. 225: 92–9

    CAS  Google Scholar 

  113. de Jong RS, Slijfer EA, Uges DR, et al. Conversion of the prodrug etoposide phosphate to etoposide in gastric juice and bile. Br J Cancer 1997; 76: 1480–3

    PubMed  Google Scholar 

  114. Newell DR. Can pharmacokinetic and pharmacodynamic studies improve cancer chemotherapy? Ann Oncol 1994; 5Suppl. 4: 9–14

    PubMed  Google Scholar 

  115. Fridborg H, Nygren P, Larsson R. Relationship between pharmacokinetic parameters in patients and cytotoxicity in vitro of standard and investigational anticancer drugs. Anticancer Drugs 1995; 6: 64–9

    PubMed  CAS  Google Scholar 

  116. Lévi F. Cancer chronotherapy. J Pharm Pharmacol 1999; 51: 891–8

    PubMed  Google Scholar 

  117. Mormont MC, Lévi F. Circadian-system alterations during cancer processes: a review. Int J Cancer 1997; 70: 241–7

    PubMed  CAS  Google Scholar 

  118. Bruguerolle B. Chronopharmacokinetics: current status. Clin Pharmacokinet 1998; 35: 83–94

    PubMed  CAS  Google Scholar 

  119. Sanders SW, Moore JG. Gastrointestinal chronopharmacology: physiology, pharmacology and therapeutic implications. Pharmacol Ther 1992; 54: 1–15

    PubMed  CAS  Google Scholar 

  120. Gardner ML, Plumb JA. Diurnal variation in the intestinal toxicity of 5-fluorouracil in the rat. Clin Sci 1981; 61: 717–22

    PubMed  CAS  Google Scholar 

  121. Ohdo S, Makinosumi T, Ishizaki T, et al. Cell cycle-dependent chronotoxicity of irinotecan hydrochloride in mice. J Pharmacol Exp Ther 1997; 283: 1383–8

    PubMed  CAS  Google Scholar 

  122. Ohdo S, Inoue K, Yukawa E, et al. Chronotoxicity of methotrexate in mice and its relation to circadian rhythm of DNA synthesis and pharmacokinetics. Jpn J Pharmacol 1997; 75: 283–90

    PubMed  CAS  Google Scholar 

  123. Lévi F, Tampellini M, Metzger G, et al. Circadian changes in mitoxantrone toxicity in mice: relationship with plasma pharmacokinetics. Int J Cancer 1994; 59: 543–7

    PubMed  Google Scholar 

  124. Song JG, Nakano S, Ohdo S, et al. Chronotoxicity and chronopharmacokinetics of methotrexate in mice: modification by feeding schedule. Jpn J Pharmacol 1993; 62: 373–8

    PubMed  CAS  Google Scholar 

  125. Schaefer HG, Heinig R, Ahr G, et al. Pharmacokinetic-pharmacodynamic modelling as a tool to evaluate the clinical relevance of a drug-food interaction for a nisoldipine controlled-release dosage form. Eur J Clin Pharmacol 1997; 51: 473–80

    PubMed  CAS  Google Scholar 

  126. Sparreboom A, Danesi R, Ando Y, et al. Pharmacogenomics of ABC transporters and its role in cancer chemotherapy. Drug Resist Updat 2003; 6: 71–84

    PubMed  CAS  Google Scholar 

  127. Lin JH, Lu AY. Interindividual variability in inhibition and induction of cytochrome P450 enzymes. Annu Rev Pharmacol Toxicol 2001; 41: 535–67

    PubMed  CAS  Google Scholar 

  128. Kruijtzer CMF, Beijnen JH, Schellens JHM. Improvement of oral drug treatment by temporary inhibition of drug transporters and/or cytochrome P450 in the gastrointestinal tract and liver: an overview. Oncologist 2002; 7: 516–30

    PubMed  CAS  Google Scholar 

  129. Ikegawa T, Ohtani H, Koyabu N, et al. Inhibition of P-glycoprotein by flavonoid derivatives in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells. Cancer Lett 2002; 177: 89–93

    PubMed  CAS  Google Scholar 

  130. Hooijberg JH, Broxterman HJ, Scheffer GL, et al. Potent interaction of flavopiridol with MRP1. Br J Cancer 1999; 81: 269–76

    PubMed  CAS  Google Scholar 

  131. Lopez-Lazaro M, Akiyama M. Flavonoids as anticancer agents: structure-activity relationship study. Curr Med Chem Anti-Canc Agents 2002; 2: 691–714

    CAS  Google Scholar 

  132. Phang JM, Poore CM, Lopaczynska J, et al. Flavonol-stimulated efflux of 7,12-dimethylbenz (a)anthracene in multidrug-resistant breast cancer cells. Cancer Res 1993; 53: 5977–81

    PubMed  CAS  Google Scholar 

  133. Critchfield JW, Welsh CJ, Phang JM, et al. Modulation of adriamycin accumulation and efflux by flavonoids in HCT-15 colon cells: activation of P-glycoprotein as a putative mechanism. Biochem Pharmacol 1994; 48: 1437–45

    PubMed  CAS  Google Scholar 

  134. Sparreboom A, van Asperen J, Mayer U, et al. Limited oral bioavailability and active epithelial excretion of paclitaxel (taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci U S A 1997; 94: 2031–5

    PubMed  CAS  Google Scholar 

  135. Leu BL, Huang JD. Inhibition of intestinal P-glycoprotein and effects on etoposide absorption. Cancer Chemother Pharmacol 1995; 35: 432–6

    PubMed  CAS  Google Scholar 

  136. Soldner A, Christians U, Susanto M, et al. Grapefruit juice activates P-glycoprotein-mediated drug transport. Pharm Res 1999; 16: 478–85

    PubMed  CAS  Google Scholar 

  137. Takanaga H, Ohnishi A, Matsuo H, et al. Inhibition of vinblastine efflux mediated by P-glycoprotein by grapefruit juice components in Caco-2 cells. Biol Pharm Bull 1998; 21: 1062–6

    PubMed  CAS  Google Scholar 

  138. Lo YL, Huang JD. Comparison of effects of natural or artificial rodent diet on etoposide absorption in rats. In Vivo 1999; 13: 51–5

    PubMed  CAS  Google Scholar 

  139. Ikegawa T, Ushigome F, Koyabu N, et al. Inhibition of P-glycoprotein by orange juice components, polymethoxyflavones in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells. Cancer Lett 2000; 160: 21–8

    PubMed  CAS  Google Scholar 

  140. Takanaga H, Ohnishi A, Yamada S, et al. Polymethoxylated flavones in orange juice are inhibitors of P-glycoprotein but not cytochrome P450 3A4. J Pharmacol Exp Ther 2000; 293(1): 230–6

    PubMed  CAS  Google Scholar 

  141. Asaum J, Matsuzaki H, Kawasak S, et al. Effects of quercetin on the cell growth and the intracellular accumulation and retention of adriamycin. Anticancer Res 2000; 20: 2477–83

    PubMed  CAS  Google Scholar 

  142. Scambia G, Ranelletti FO, Panici PB, et al. Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast-cancer cell line: P-glycoprotein as a possible target. Cancer Chemother Pharmacol 1994; 34: 459–64

    PubMed  CAS  Google Scholar 

  143. Sadzuka Y, Sugiyama T, Sonobe T. Efficacies of tea components on doxorubicin induced antitumor activity and reversal of multidrug resistance. Toxicol Lett 2000; 114: 155–62

    PubMed  CAS  Google Scholar 

  144. Zhang S, Morris ME. Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on P-glycoprotein-mediated transport. J Pharmacol Exp Ther 2003; 304: 1258–67

    PubMed  CAS  Google Scholar 

  145. Christensen JG, LeBlanc GA. Reversal of multidrug resistance in vivo by dietary administration of the phytochemical indole-3-carbinol. Cancer Res 1996; 56: 574–81

    PubMed  CAS  Google Scholar 

  146. Plouzek CA, Ciolino HP, Clarke R, et al. Inhibition of P-glycoprotein activity and reversal of multidrug resistance in vitro by rosemary extract. Eur J Cancer 1999; 35: 1541–5

    PubMed  CAS  Google Scholar 

  147. Leslie EM, Mao Q, Oleschuk CJ, et al. Modulation of multidrug resistance protein 1 (MRP1/ABCC1) transport and ATPase activities by interaction with dietary flavonoids. Mol Pharmacol 2001; 59: 1171–80

    PubMed  CAS  Google Scholar 

  148. Hooijberg JH, Broxterman HJ, Heijn M, et al. Modulation by (iso)flavonoids of the ATPase activity of the multidrug resistance protein. FEBS Lett 1997; 413: 344–8

    PubMed  CAS  Google Scholar 

  149. Nguyen H, Zhang S, Morris ME. Effect of flavonoids on MRP1-mediated transport in Panc-1 cells. J Pharm Sci 2003; 92: 250–7

    PubMed  CAS  Google Scholar 

  150. Jager W, Winter O, Halper B, et al. Modulation of liver canalicular transport processes by the tyrosine-kinase inhibitor genistein: implications of genistein metabolism in the rat. Hepatology 1997; 26: 1467–76

    PubMed  CAS  Google Scholar 

  151. Ohnishi A, Matsuo H, Yamada S, et al. Effect of furanocoumarin derivatives in grapefruit juice on the uptake of vinblastine by Caco-2 cells and on the activity of cytochrome P450 3A4. Br J Pharmacol 2000; 130: 1369–77

    PubMed  CAS  Google Scholar 

  152. Dresser GK, Bailey DG, Leake BF, et al. Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine. Clin Pharmacol Ther 2002; 71: 11–20

    PubMed  CAS  Google Scholar 

  153. Reif S, Nicolson MC, Bisset D, et al. Effect of grapefruit juice intake on etoposide bioavailability. Eur J Clin Pharmacol 2002; 58: 491–4

    PubMed  CAS  Google Scholar 

  154. Mazzanti R, Fantappie O, Kamimoto Y, et al. Bile acid inhibition of P-glycoprotein-mediated transport in multidrug-resistant cells and rat liver canalicular membrane vesicles. Hepatology 1994; 20: 170–6

    PubMed  CAS  Google Scholar 

  155. Bates SE, Currier SJ, Alvarez M, et al. Modulation of P-glycoprotein phosphorylation and drug transport by sodium butyrate. Biochemistry 1992; 31: 6366–72

    PubMed  CAS  Google Scholar 

  156. Robert J. Pharmacokinetic mechanisms of resistance to anti-cancer medications [in French]. Bull Cancer 1994; 81 Suppl. 2: 78–81S

    Google Scholar 

  157. Poplack DG, Balis FM, Zimm S. The pharmacology of orally administered chemotherapy: a reappraisal. Cancer 1986; 58 (2 Suppl.): 473–80

    PubMed  CAS  Google Scholar 

  158. Maxwell MB. Re-examining the dietary restrictions with procarbazine (an MAOI). Cancer Nurs 1980; 3: 451–7

    PubMed  CAS  Google Scholar 

  159. Wiebe VJ, Benz CC, DeGregorio MW. Clinical pharmacokinetics of drugs used in the treatment of breast cancer. Clin Pharmacokinet 1988; 15: 180–93

    PubMed  CAS  Google Scholar 

  160. de Vries EG, Meyer C, Strubbe M, et al. Influence of various beverages on urine acid output. Cancer Res 1986; 46: 430–2

    PubMed  Google Scholar 

  161. Araujo C, Cervellino J, Miles H, et al. Use of mesna as antitumor agent: a phase II GETLAC study [abstract]. 35th Annual Meeting of the American Society of Clinical Oncology; 1999 May 15–18; Atlanta, A779

    Google Scholar 

  162. Bracke ME, Depypere HT, Boterberg T, et al. Influence of tangeretin on tamoxifen’s therapeutic benefit in mammary cancer. J Natl Cancer Inst 1999; 91: 354–9

    PubMed  CAS  Google Scholar 

  163. Bjornsson TD, Huang AT, Roth P, et al. Effects of high-dose cancer chemotherapy on the absorption of digoxin in two different formulations. Clin Pharmacol Ther 1986; 39: 25–8

    PubMed  CAS  Google Scholar 

  164. Johnson EJ, MacGowan AP, Potter MN, et al. Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy. J Antimicrob Chemother 1990; 25: 837–42

    PubMed  CAS  Google Scholar 

  165. Brown NM, White LO, Blundell EL, et al. Absorption of oral ofloxacin after cytotoxic chemotherapy for haematological malignancy. J Antimicrob Chemother 1993; 32: 117–22

    PubMed  CAS  Google Scholar 

  166. Sokol GH, Greenblatt DJ, Lloyd BL, et al. Effect of abdominal radiation therapy on drug absorption in humans. J Clin Pharmacol 1978; 18: 388–96

    PubMed  CAS  Google Scholar 

  167. Kuhlmann J, Zilly W, Wilke J. Effects of cytostatic drugs on plasma level and renal excretion of beta-acetyldigoxin. Clin Pharmacol Ther 1981; 30: 518–27

    PubMed  CAS  Google Scholar 

  168. Hsyu PH, Pritchard JF, Bozigian HP, et al. Oral ondansetron pharmacokinetics: the effect of chemotherapy. J Clin Pharmacol 1994; 34: 767–73

    PubMed  CAS  Google Scholar 

  169. Hurter T, Reis HE, Borchard F. Disorders of intestinal absorption in patients treated with cytostatic chemotherapy [in German]. Z Gastroenterol 1989; 27: 606–10

    PubMed  CAS  Google Scholar 

  170. Lindenbaum J. Greater bioavailability of digoxin solution in capsules: studies in the postprandial state. Clin Pharmacol Ther 1977; 21: 278–82

    PubMed  CAS  Google Scholar 

  171. Neuvonen PJ, Kivisto KT, Lehto P. Interference of dairy products with the absorption of ciprofloxacin. Clin Pharmacol Ther 1991; 50: 498–502

    PubMed  CAS  Google Scholar 

  172. Verho M, Malerczyk V, Dagrosa E, et al. The effect of food on the pharmacokinetics of ofloxacin. Curr Med Res Opin 1986; 10: 166–71

    PubMed  CAS  Google Scholar 

  173. Murry DJ, Riva L, Poplack DG. Impact of nutrition on pharmacokinetics of anti-neoplastic agents. Int J Cancer 1998; 11 Suppl.: 48–51

    CAS  Google Scholar 

  174. Henriksson R, Rogo KO, Grankvist K. Interaction between cytostatics and nutrients. Med Oncol Tumor Pharmacother 1991; 8: 79–86

    PubMed  CAS  Google Scholar 

  175. BC Cancer Agency, Canada. BCCA cancer drug manual [online]. Available from URL: http://www.bccancer.bc.ca/HPI/DrugDatabase [Accessed 2004 Nov 9]

  176. Wolf M, Holle R, Hans K, et al. Analysis of prognostic factors in 766 patients with small cell lung cancer (SCLC): the role of sex as a predictor for survival. Br J Cancer 1991; 63: 986–92

    PubMed  CAS  Google Scholar 

  177. Cohen SM, Ohnuma T, Ambinder EP, et al. Lomustine, bleomycin, and cisplatin in patients with metastatic malignant melanoma. Cancer Treat Rep 1986; 70: 688–9

    PubMed  CAS  Google Scholar 

  178. Luger SM, Kirkwood JM, Ernstoff MS, et al. High-dose cisplatin and dacarbazine in the treatment of metastatic melanoma. J Natl Cancer Inst 1990; 82: 1934–7

    PubMed  CAS  Google Scholar 

  179. Fagan TC, Oexmann MJ. Effects of high protein, high carbohydrate, and high fat diets on laboratory parameters. J Am Coll Nutr 1987; 6: 333–43

    PubMed  CAS  Google Scholar 

  180. Takahashi T, Kono K, Yamaguchi T. Enhancement of the cancer chemotherapeutic effect by anticancer agents in the form of fat emulsion. Tohoku J Exp Med 1977; 123: 235–46

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was presented in part at the Annual Scientific Meeting of the International Society of Preventive Oncology, 28–31 October 2000, Geneva, Switzerland. Brahma Singh gratefully acknowledges the financial support of the College of Pharmacy, St John’s University, Jamaica, New York, USA, in the form of a doctoral fellowship.

The authors have no current or potential conflicts of interest that are directly relevant to the contents of this manuscript.

Author information

Authors and Affiliations

  1. Department of Pharmacy and Administrative Sciences, College of Pharmacy and Allied Health Professions, St John’s University, Jamaica, New York, USA

    Brahma N. Singh & Bimal K. Malhotra

  2. Department of Clinical Sciences, Pfizer Inc., New York, New York, USA

    Bimal K. Malhotra

Authors
  1. Brahma N. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bimal K. Malhotra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brahma N. Singh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Singh, B.N., Malhotra, B.K. Effects of Food on the Clinical Pharmacokinetics of Anticancer Agents. Clin Pharmacokinet 43, 1127–1156 (2004). https://doi.org/10.2165/00003088-200443150-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-200443150-00005

Keywords

Search

Navigation