Intraperitoneal chemotherapy

  • M. F. Flessner
  • R. L. Dedrick


A wide variety of therapeutic drugs are administered into the peritoneal cavity as a portal of entry to the body and as a localized treatment. Because of intravenous access problems in neonates, transfusion of packed red blood cells was one of the earliest uses of intraperitoneal (i.p.) therapy [1, 2]. Insulin is often placed in the dialysate in order to treat glucose intolerance during peritoneal dialysis [3], and i.p. insulin delivery is currently undergoing investigation as a means of long-term therapy in diabetes [4]. Erythropoietin, prescribed as replacement therapy for the anaemia related to end-stage renal disease (ESRD), has recently been administered intraperitoneally [5, 6]. In contrast to these forms of i.p. therapy which are designed to treat systemic illnesses, antibacterial agents are injected intraperitoneally in order to treat peritonitis [7, 8]. In the past 20 years i.p. chemotherapy has increasingly been evaluated for treatment of malignancies localized to the peritoneal cavity [9–22].


Peritoneal Dialysis Peritoneal Cavity Peritoneal Fluid Continuous Ambulatory Peritoneal Dialysis Intraperitoneal Chemotherapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cole WCC, Montgomery JC. Intraperitoneal blood transfusion. Amer J Dis Child 1929; 37: 497–510.Google Scholar
  2. 2.
    Clausen J. Studies on the effects of intraperitoneal blood transfusion. Acta Paediatr, Stockholm 1940; 27: 24–31.Google Scholar
  3. 3.
    Rubin JA, Reed V, Adair C, Bower J, Klein E. Effect of intraperitoneal insulin on solute kinetics in CAPD: insulin kinetics in CAPD. Am J Med Sci 1986; 291: 81–7.PubMedGoogle Scholar
  4. 4.
    Pitt HA, Saudek CD, Zacur HA. Long-term intraperitoneal insulin delivery. Ann Surg 1992; 216: 483–92.PubMedGoogle Scholar
  5. 5.
    Bargman JM, Jones JE, Petro JM. The pharmacokinetics of intraperitoneal erythropoietin administered undiluted and diluted in dilaysate. Petit Dial Int 1992; 12: 369–72.Google Scholar
  6. 6.
    Reddingius RE, de Boer AW, Scroder CH, Willems JL, Monnens LAH. Increase of the bioavailability of intraperitoneal erythropoietin in children on peritoneal dialysis by administration in small dialysis bags. Petit Dial Int 1997; 17: 467–70.Google Scholar
  7. 7.
    Hirszel P, Lameire N, Bogaert M. Pharmacologic alterations of peritoneal transport rates and pharmacokinetics of the peritoneum. In: Gokal R, Nolph KD, eds. The Textbook of Peritoneal Dialysis. Dordrecht: Kluwer, 1994, pp. 161–232.Google Scholar
  8. 8.
    Keane WF, Alexander SR, Bailie GR et al Peritoneal dialysis-related peritonitis treatment recommendations: 1996 update. Petit Dial Int 1996; 16: 557–73.Google Scholar
  9. 9.
    Jones RB, Myers CE, Guarino AM, Dedrick RL, Hubbard SM, DeVita VT. High volume intraperitoneal chemotherapy (Belly Bath’) for ovarian cancer. Cancer Chemother Pharm 1978; 1: 161–6.Google Scholar
  10. 10.
    Speyer JL, Collins JM, Dedrick RL et al Phase I and pharmacological studies of 5-fluorouracil administered intraperitoneally. Canc Res 1980; 40: 567–72.Google Scholar
  11. 11.
    Speyer JL, Sugarbaker PH, Collins JM, Dedrick RL, Klecker RW, Jr, Myers CE. Portal levels and hepatic clearance of 5-fluorouracil after intraperitoneal administration in humans. Cancer Res 1981; 41: 1916–22.PubMedGoogle Scholar
  12. 12.
    Markman M. Intraperitoneal therapy for ovarian cancer. Semin Oncol 1998; 25: 356–60.PubMedGoogle Scholar
  13. 13.
    Ozols RF, Young RC, Speyer JL et al Phase I and pharmacological studies of adriamycin administered intraperitoneally to patients with ovarian cancer. Cancer Res 1982; 42: 4265–9.PubMedGoogle Scholar
  14. 14.
    Gianni L, Jenkins JF, Greene RF, Lichter AS, Myers CE, Collins JM. Pharmacokinetics of the hypoxic radiosensitizers misonidazole and demethylmisonidazole after intraperitoneal administration in humans. Cancer Res 1983; 43: 913–16.PubMedGoogle Scholar
  15. 15.
    Arbuck SG, Trave F, Douglas Jr HO, Nava H, Zakrzewkski S, Rustum YM. Phase I and pharmacologic studies of intraperitoneal leucovorin and 5-fluorouracil in patients with advanced cancer. J Clin Oncol 1986; 4: 1510–17.PubMedGoogle Scholar
  16. 16.
    Urba WJ, Clark JW, Steis RG et al Intraperitoneal lymphokine-activated killer cell/interleukin-2 therapy in patients with intra-abdominal cancer: immunologic considerations. J Nat Cancer Inst 1989; 81: 602–11.PubMedGoogle Scholar
  17. 17.
    Markman M, Hakes T, Reichmann B, Hoskins W, Rubin S, Lewis Jr JL. Intraperitoneal versus intravenous cisplatinbased therapy in small-volume residual refractory ovarian cancer: evidence supporting an advantage for local drug delivery. Reg Cancer Treat 1990; 3: 10–12.Google Scholar
  18. 18.
    Alberts DS, Liu PY, Hannigan EV et al Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 1996; 335: 1950–5.PubMedGoogle Scholar
  19. 19.
    Markman M, Rowinsky E, Hakes T et al Phase I trial of intraperitoneal taxol: a Gynecologic Oncology Group Study. J Clin Oncol 1992; 10: 1485–1491.PubMedGoogle Scholar
  20. 20.
    Markman M, Brady MF, Spirtos NM, Hanjani P, Rubin SC. Phase II trial of intraperitoneal paclitaxel in carcinoma of the ovary, tube, and peritoneum: a Gynecologic Oncology Group study. J Clin Oncol 1998; 16: 2620–4.PubMedGoogle Scholar
  21. 21.
    Muggia FM, Liu PY, Alberts DS et al Intraperitoneal mitoxantrone or floxuridine: effects on time-to-failure and survival in patients with minimal residual ovarian cancer after second-look laparotomy–a randomized phase II study by the Southwest Oncology Group. Gynecol Oncol 1996; 61: 395–402.PubMedGoogle Scholar
  22. 22.
    Howell SB, Pfeifle CE, Wung WE, Olshen RA. Intraperitoneal cis-diamminedichloroplatinum with systemic thiosulfate protection. Cancer Res 1983; 43: 1426–31.PubMedGoogle Scholar
  23. 23.
    Dedrick RL. Interspecies scaling of regional drug delivery. J Pharm Sci 1986; 75: 1047–52.PubMedGoogle Scholar
  24. 24.
    Crafts RC. A Textbook of Human Anatomy, 2nd edn. New York: John Wiley, 1979, pp. 213–345.Google Scholar
  25. 25.
    Leak LB, Rahil K. Permeability of the diaphragmatic mesothelium: the ultrastructural basis for `stomata’. Am J Anat 1978; 151: 557–94.PubMedGoogle Scholar
  26. 26.
    Bettendorf U. Lymph flow mechanism of the subperitoneal diaphragmatic lymphatics. Lymphology 1978; 11: 111–16.PubMedGoogle Scholar
  27. 27.
    Allen L. On the penetrability of the lymphatics of the diaphragm. Anat Rec 1956; 124: 639–58.PubMedGoogle Scholar
  28. 28.
    Yoffey JM, Courtice FC. Lymphatics, Lymph, and the Lymphomyeloid Complex. New York: Academic Press, 1970.Google Scholar
  29. 29.
    Flessner MF, Parker RJ, Sieber SM. Peritoneal lymphatic uptake of fibrinogen and erythrocytes in the rat. Am J Physiol 1983; 244: H89–96.PubMedGoogle Scholar
  30. 30.
    Abernathy NJ, Chin W, Hay JB, Rodela H, Oreopoulos D, Johnston MG. Lymphatic drainage of the peritoneal cavity in sheep. Am J Physiol 1991; 260: F353–8.Google Scholar
  31. 31.
    Flessner MF, Dedrick RL, Reynolds JC. Bidirectional peritoneal transport of immunoglobulin in rats: compartmental kinetics. Am J Physiol 1992; 262: F275–87.PubMedGoogle Scholar
  32. 32.
    Pearson CM. Circulation in skeletal muscle. In: Abramson DI, ed. Blood Vessels and Lymphatics. New York: Academic Press, 1962, pp. 520–1.Google Scholar
  33. 33.
    Flessner MF, Dedrick RL, Reynolds JC. Bidirectional peritoneal transport of immunoglobulin in rats: tissue concentration profiles. Am J Physiol 1992; 263: F15–23.PubMedGoogle Scholar
  34. 34.
    Rubm J, Clawson M, Planch A, Jones Q. Measurements of peritoneal surface area in man and rat. Am J Med Sci 1988; 295: 453–8.Google Scholar
  35. 35.
    Esperanca MJ, Collins DL. Peritoneal dialysis efficiency in relation to body weight. J Pediatr Surg 1966; 1: 162–9.Google Scholar
  36. 36.
    Ludwig J. Current Methods of Autopsy Practice. Philadelphia: WB Saunders, 1972.Google Scholar
  37. 37.
    Rhodin JAG. Histology: A Text and Atlas. New York: Oxford University Press, 1974.Google Scholar
  38. 38.
    Richardson KC. Illustrations of Light Microscopical Preparations from Various Tissues and Organs. Baltimore: University of Maryland School of Medicine, 1976.Google Scholar
  39. 39.
    diFiore MSH. Atlas of Human Histology. Philadelphia: Lea and Febiger, 1981.Google Scholar
  40. 40.
    Rubin J, Jones Q, Planch A, Stanek K. Systems of membranes involved in peritoneal dialysis. J Lab Clin Med 1987; 110: 448–53.PubMedGoogle Scholar
  41. 41.
    Vetterlein F, Schmidt G. Functional capillary density in skeletal muscle during vasodilation induced by isoprenaline and muscular exercise. Microvasc Res 1980; 20: 156–64.PubMedGoogle Scholar
  42. 42.
    Guyton AC. Textbook of Medical Physiology, 6th edn. Philadelphia: WB Saunders, 1981, p. 349.Google Scholar
  43. 43.
    Mapleson WW. An electric analogue for uptake and exchange of inert gases and other agents. J Appl Physiol 1963; 18: 197–204.PubMedGoogle Scholar
  44. 44.
    Bonaccorsi A, Dejana E, Quintana A. Organ blood flow measured with microspheres in the unanesthetized rat: effects of three room temperatures. J Pharmacol Meth 1978; 1: 321–8.Google Scholar
  45. 45.
    Grim E. The flow of blood in the mesenteric vessels. In: Hamilton WF, Dow P, eds. Handbook of Physiology. vol. II, sect 2, Washington: American Physiological Society, 1963, pp. 1443–56.Google Scholar
  46. 46.
    Chow CC, Grassmick B. Motility and blood flow distribution within the wall of the gastrointestinal tract. Am J Physiol 1978; 235: H34–9.Google Scholar
  47. 47.
    Crandall LA Jr, Barker SB, Graham DG. A study of the lymph flow from a patient with thoracic duct fistula. Gastroenterology 1943; 1: 1040.Google Scholar
  48. 48.
    Courtice FC, Simonds WJ, Steinbeck AW. Some investigations on lymph from a thoracic duct fistula in man. Austral J Exp Biol Med Sci 1951; 29: 201.Google Scholar
  49. 49.
    O’Morchoe CCC, O’Morchoe DJ, Holmes MJ, Jarosz HM. Flow of renal hilar lymph during volume expansion and saline diuresis. Lymphology 1978; 11: 27–31.PubMedGoogle Scholar
  50. 50.
    Shad H, Brechtelsbauer H. Thoracic duct lymph in conscious dog at rest and during changes of physical activity. Pfluegers Arch 1978; 367: 235–40.Google Scholar
  51. 51.
    Morris B. The exchange of protein between the plasma and the liver and intestinal lymph. Q J Exp Physiol 1956; 41; 326.PubMedGoogle Scholar
  52. 52.
    Yoffey JM, Courtice FC. Lymphatics, Lymph, and Lymphoid Tissue. Cambridge, MA: Harvard University Press, 1956: pp. 121–35.Google Scholar
  53. 53.
    Tran L, Rodela H, Abernethy NJ et al Lymphatic drainage of hypertonic solution from peritoneal cavity of anesthetized and conscious sheep. J Appl Physiol 1993; 74: 859–67.PubMedGoogle Scholar
  54. 54.
    Daugirdas JT, Ing TS, Gandhi VC, Hano JE, Chen WT, Yuan L. Kinetics of peritoneal fluid absorption in patients with chronic renal failure. J Lab Clin Med 1980; 85: 351–61.Google Scholar
  55. 55.
    Rippe B, Stelin G, Ahlmen J. Lymph flow from the peritoneal cavity in CAPD patients. In: Maher JF, Winchester JF, eds. Frontiers in Peritoneal Dialysis. New York: Field, Rich, 1986, pp. 24–30.Google Scholar
  56. 56.
    Dykes PW, Jones JH. Albumin exchange between plasma and ascites fluid. Clin Sci 1964; 34: 185–97.Google Scholar
  57. 57.
    Mactier RA, Khanna R, Twardowski Z, Nolph KD. Role of peritoneal cavity lymphatic absorption in peritoneal dialysis. Kidney Int 1987; 32: 165–74.PubMedGoogle Scholar
  58. 58.
    Zink J, Greenway CV. Control of ascites absorption in anesthetized cats: effects of intraperitoneal pressure, protein, and furosemide diuresis. Gastroenterology 1974; 73: 1119–24.Google Scholar
  59. 59.
    Flessner MF, Schwab A. Pressure threshold for fluid loss from the peritoneal cavity. Am J Physiol 1992; 270: F377–90.Google Scholar
  60. 60.
    Nolph KD, Mactier R, Khanna R, Twardowski ZJ, Moore H, McGary T. The kinetics of ultrafiltration during peritoneal dialysis: the role of lymphatics. Kidney Int 1987; 32: 219–26.PubMedGoogle Scholar
  61. 61.
    Flessner MF. Net ultrafiltration in peritoneal dialysis: role of direct fluid absorption into peritoneal tissue. Blood Purif 1992; 10: 136–47.Google Scholar
  62. 62.
    Dedrick RL, Flessner MF, Collins JM, Schultz JS. Is the peritoneum a membrane? ASAIO J 1982; 5: 1–8.Google Scholar
  63. 63.
    Chagnac A, Herskovitz P, Weinstein T et al The peritoneal membrane in peritoneal dialysis patients: estimation of its functional surface area by applying stereological methods to CT scans. J Am Soc Nephrol 1999; 10: 342–6.PubMedGoogle Scholar
  64. 64.
    Putiloff PV. Materials for the study of the laws of growth of the human body in relation to the surface areas of different systems; the trial on Russian subjects of planigraphic anatomy as a means for exact anthropometry - one of the problems of anthropology. Report of Dr P. V. Putiloff at the meeting of the Siberian Branch of the Russian Geographic Society, 29 October 1884, Omsk, 1886.Google Scholar
  65. 65.
    Dedrick RL, Myers CE, Bungay PM, DeVita VT. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep 1978; 61: 1–11.Google Scholar
  66. 66.
    Rippe B, Stelin G, Ahlmen J. Basal permeability of the peritoneal membrane during continuous ambulatory peritoneal dialysis (CAPD). In: Maher J, ed. Advances in Peritoneal Dialysis, 1981. Amsterdam: Excerpta Medica, 1981, pp. 5–9.Google Scholar
  67. 67.
    Krediet RT, Struijk DG, Koomen GCM et al Peritoneal transport of macromolecules in patients on CAPD. Contrib Nephrol 1991; 89: 161–74.PubMedGoogle Scholar
  68. 68.
    Keshaviah P, Emerson PF, Vonesh EF, Brandes JC. Relationship between body size, fill volume, and mass transfer area coefficient in peritoneal dialysis. J Am Soc Nephrol 1994; 4: 1820–6.PubMedGoogle Scholar
  69. 69.
    Flessner MF. Small solute transport across specific peritoneal tissue surfaces in the rat. J Am Soc Nephrol 1996; 7: 225–33.PubMedGoogle Scholar
  70. 70.
    Levitt MD, Kneip JM, Overdahl MC. Influence of shaking on peritoneal transfer in rats. Kidney Int 1989; 35: 1145–50.PubMedGoogle Scholar
  71. 71.
    Zakaria ER, Carlsson O, Rippe B. Limitation of small-solute exchange across the visceral peritoneum: effects of vibration. Perit Dial Int 1996; 17: 72–9.Google Scholar
  72. 72.
    Dedrick RL, Flessner MF. Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer Inst 1997; 89: 480–7.PubMedGoogle Scholar
  73. 73.
    Steller MA, Egorin MJ, Trimble EL et al A pilot phase I trial of continuous hyperthermic peritoneal perfusion (CHPP) with high-dose carboplatin (CBDCA) as primary treatment of patients with small volume residual ovarian cancer. Cancer Chemother Pharmacol 1999; 43: 106–14.PubMedGoogle Scholar
  74. 74.
    Kim M, Lofthouse J, Flessner MF. Blood flow limitations of solute transport across the visceral peritoneum. J Am Soc Nephrol 1997; 8: 1946–50.PubMedGoogle Scholar
  75. 75.
    Torres IJ, Litterst CL, Guarino AM. Transport of model compounds across the peritoneal membrane in the rat. Pharmacology 1978; 17: 330–40.PubMedGoogle Scholar
  76. 76.
    Wikes AD, Howell SB. Pharmacokinetics of hexamethylmelamine administered via the ip route in an oil emulsion vehicle. Cancer Treat Rep 1985; 69: 657–62.Google Scholar
  77. 77.
    Lewis C, Lawson N, Rankin EM et al Phase I and pharmacokinetic study of intraperitoneal thioTEPA in patients with ovarian cancer. Cancer Chemother Pharmacol 1990; 26: 283–7.PubMedGoogle Scholar
  78. 78.
    Aune S. Transperitoneal exchange. II. Peritoneal blood flow estimated by hydrogen gas clearance. Scand J Gastroenterol 1970; 5: 99–104.PubMedGoogle Scholar
  79. 79.
    Flessner MF. Transport of water soluble solutes between the peritoneal cavity and the plasma in the rat. (Dissertation.) Ann Arbor, MI: Department of Chemical Engineering, University of Michigan, 1981.Google Scholar
  80. 80.
    Grzegorzewska AE, Moore HL, Nolph KD, Chen TW. Ultrafiltration and effective peritoneal blood flow during peritoneal dialysis in the rat. Kidney Int 1991; 39: 608–17.PubMedGoogle Scholar
  81. 81.
    Collins JM. Inert gas exchange of subcutaneous and intraperitoneal gas pockets in piglets. Resp Phys 1981; 46: 391–404.Google Scholar
  82. 82.
    Demissachew H, Lofthouse J, Flessner MF. Tissue sources and blood flow limitations of osmotic water flow across the peritoneum. J Am Soc Nephrol 1999; 10: 347–53.PubMedGoogle Scholar
  83. 83.
    Zakaria ER, Carlsson O, Rippe B. Liver is not essential for solute transport during peritoneal dialysis. Kidney Int 1996; 50: 298–303.PubMedGoogle Scholar
  84. 84.
    Erb RW, Greene JA Jr, Weller JM. Peritoneal dialysis during hemorrhagic shock. J Appl Physiol 1967; 22: 131–5.Google Scholar
  85. 85.
    Pitts RF. Physiology of the Kidney and Body Fluids. Chicago: Year Book Medical Publishers, 1963, p. 63.Google Scholar
  86. 86.
    Lukas G, Brindle SD, Greengard P. The route of absorption of intraperitonelly administered compounds. J Pharmacol Exp Ther 1971; 178: 562–6.PubMedGoogle Scholar
  87. 87.
    Myers CE, Collins JM. Pharmacology of intraperitoneal chemotherapy. Cancer Invest 1983; 1: 395–407.PubMedGoogle Scholar
  88. 88.
    Brenner DE. Intraperitoneal chemotherapy: a review. J Clin Oncol 1986; 4: 1135–47.PubMedGoogle Scholar
  89. 89.
    Los G, McVie JG. Experimental and clinical status of intraperitoneal chemotherapy. Eur J Cancer 1990; 26: 755–62.PubMedGoogle Scholar
  90. 90.
    Markman M, Reichman B, Hakes T et al Impact on survival of surgically defined favorable responses to salvage intraperitoneal chemotherapy in small-volume residual ovaian cancer. J Clin Oncol 1992; 10: 1479–84.PubMedGoogle Scholar
  91. 91.
    Ozols RF. Intraperitoneal chemotherapy. Current Prob Cancer 1992; 16: 99–101.Google Scholar
  92. 92.
    Alberts DS, Liu PY, Hannigan EV et al Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 1996; 335: 1950–5.PubMedGoogle Scholar
  93. 93.
    Farris FF, King FG, Dedrick RL, Litterst CL. Physiological model for the pharmacokinetics of cis-dichlorodiammineplatinum(n) (DDP) in the tumored rat. J Pharmacokin Biopharmacol 1985; 13: 13–39.Google Scholar
  94. 94.
    King FG, Dedrick RL, Farris FF. Physiological pharmacokinetic modeling of cis-dichlorodiammineplatinum(n) (DDP) in several species. J Pharmacokin Biopharm 1986; 14: 131–55.Google Scholar
  95. 95.
    King FG, Dedrick RL. Physiological pharmacokinetic parameters for cis-dichlorodiammineplatinum(n) (DDP) in the mouse. J Pharmacokin Biopharmacol 1992; 20: 95–9.Google Scholar
  96. 96.
    Goel R, Cleary SM, Horton C et al Effect of sodium thiosulfate on the pharmacokinetics and toxicity of cisplatin. J Nat Cancer Inst 1989; 81: 1552–60.PubMedGoogle Scholar
  97. 97.
    Piccart MJ, Abrams J, Dodian PF et al Intraperitoneal chemotherapy with cisplatin and melphalan. J Natl Cancer Inst 1988; 80: 1118–24.PubMedGoogle Scholar
  98. 98.
    Los G, Mutsaers PHA, van der Vigh WJF, Baldew GS, de Graaf PW, McVie JG. Direct diffusion of cis-diamminedichloroplatinum(n) in intraperitoneal rat tumors after intraperitoneal chemotherapy: a comparison with systemic chemotherapy. Cancer Res 1989; 49: 3380–4.PubMedGoogle Scholar
  99. 99.
    Flessner MF, Fenstermacher JD, Dedrick RL, Blasberg RG. A distributed model of peritoneal-plasma transport: tissue concentration gradients. Am J Physiol 1985; 248: F425–35.PubMedGoogle Scholar
  100. 100.
    Morrison PF, Dedrick RL. Transport of cisplatin in rat brain following microinfusion: an analysis. J Pharm Sci 1986; 75: 120–8.PubMedGoogle Scholar
  101. 101.
    Pretorius RG, Petrilli ES, Kean C, Ford LC, Hoeschele JD, Lagasse LD. Comparison of the iv and ip routes of cisplatin in dogs. Cancer Treat Rep 1981; 65: 1055–62.PubMedGoogle Scholar
  102. 102.
    Chabner BA. Fluorinated pyrimidines. In: Chabner B, ed. Pharmacologic Principles of Cancer Treatment. Philadelphia: WB Saunders, 1982, pp. 183–212.Google Scholar
  103. 103.
    Collins JM, Dedrick RL, King FG, Speyer JL, Myers CE. Nonlinear pharmacokinetic models for 5-fluorouracil in man: intravenous and intraperitoneal routes. Clin Pharmacol Ther 1980; 28: 235–46.PubMedGoogle Scholar
  104. 104.
    Sugarbaker PH, Graves T, DeBruijn EA et al Early postoperative intraperitoneal chemotherapy as an adjuvant therapy to surgery for peritoneal carcinomatosis from gastrointestinal cancer: pharmacological studies. Cancer Res 1990; 50: 5790–4.PubMedGoogle Scholar
  105. 105.
    Archer SG, McCulloch RK, Gray BN. A comparative study of the pharmacokinetics of continuous portal vein infusion versus intraperitoneal infusion of 5-fluorouracil. Reg Cancer Treat 1989; 2: 105–11.Google Scholar
  106. 106.
    Gianola FJ, Sugarbaker PH, Barofsky I, White DE, Meyers CE. Toxicity studies of adjuvant intravenous versus intraperitoneal 5-FU in patients with advanced primary colon or rectal cancer. Am J Clin Oncol 1986; 9: 403–10.PubMedGoogle Scholar
  107. 107.
    Collins JM, Dedrick RL, Flessner MF, Guarino AM. Concentration-dependent disappearance of fluorouracil from peritoneal fluid in the rat: experimental observations and distributed modeling. J Pharm Sci 1982; 71: 735–8.PubMedGoogle Scholar
  108. 108.
    Cutler NR, Narang PK, Lesko LJ, Ninos M, Power M. Vancomycin disposition: the importance of age. Clin Pharmacol Ther 1984; 36: 803–10.PubMedGoogle Scholar
  109. 109.
    Moellering RC. Pharmacokinetics of vancomycin. J Antimicrob Chemother 1984; 14 (suppl.): D43–52.Google Scholar
  110. 110.
    Matzke GR, McGory RW, Halstenson CE, Keane WF. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrob Agents Chemother 1984; 25: 433–7.PubMedGoogle Scholar
  111. 111.
    Rotschafer JC, Crossley K, Zaske DE, Mead K, Sawcuk RJ, Solem LD. Pharmacokinetics of vancomycin: observations in 28 patients and dosage recommendations. Antimicrob Agents Chemother 1982; 22: 391–4.PubMedGoogle Scholar
  112. 112.
    Nielsen HE, Hansen HE, Korsager B, Skov PE. Renal excretion of vancomycin in kidney disease. Acta Med Scand 1975; 197: 261–4.PubMedGoogle Scholar
  113. 113.
    Cunha BA, Ristuccia AM. Clinical usefulness of vancomycin. Clin Pharmacol 1983; 2: 417–24.Google Scholar
  114. 114.
    Bunke CM, Aronoff GR, Brier ME, Sloan RS, Luft FC. Vancomycin kinetics during continuous ambulatory peritoneal dialysis. Clin Pharmacol Ther 1983; 34: 621–37.Google Scholar
  115. 115.
    Guyton AC. Textbook of Medical Physiology, 6th edn. Philadelphia: WB Saunders, 1981, p. 959.Google Scholar
  116. 116.
    Lamer J. Insulin and oral hypoglycemic drugs and glucagon. In: Gilman AG, Goodman LS, Rall TW, Murad F, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 7th edn. New York: Macmillan, 1985, pp. 1490–503.Google Scholar
  117. 117.
    Duckworth WC. Insulin degradation: mechanisms, products, and significance. Endocrine Rev 1988; 9: 319–45.Google Scholar
  118. 118.
    Duckworth WC, Saudek CD, Henry RR. Why intraperitoneal delivery of insulin with implantable pumps in NIDDM? Diabetes 1992; 41: 657–61.PubMedGoogle Scholar
  119. 119.
    Shapiro DJ, Blumenkrantz MJ, Levin SR, Coburn JW. Absorption and action of insulin added to peritoneal dialysate in dogs. Nephron 1979; 23: 174–80.PubMedGoogle Scholar
  120. 120.
    Scarpioni L, Ballocchi S. Castelli A. Scarpioni R. Insulin therapy in uremic diabetic patients on continuous ambulatory peritoneal dialysis; comparison of intraperitoneal and subcutaneous administration. Perit Dial Int 1994; 14: 127–31.PubMedGoogle Scholar
  121. 121.
    Fuss M, Bergans A, Brauman H et al. î25I-insulin metabolism in chronic renal failure treated by renal transplantation. Kidney Int 1974; 5: 372–7.PubMedGoogle Scholar
  122. 122.
    Navalesi R, Pilo A, Lenzi S, Donato L. Insulin metabolism in chronic uremia and in the anephric state: effect of the dialytic treatment. J Clin Endocrinol Metab 1975; 40: 70–85.PubMedGoogle Scholar
  123. 123.
    Wideroe T-E, Smeby LC, Berg KJ, Jorstad S, Svart TM. Intraperitoneal (125I) insulin absorption during intermittent and continous peritoneal dialysis. Kidney Int 1983; 23: 22–8.PubMedGoogle Scholar
  124. 124.
    Micossi P, Cristallo M, Librenti MC et al Free-insulin profiles after intraperitoneal, intramuscular, and subcutaneous insulin adminstration. Diabet Care 1986; 9: 575–8.Google Scholar
  125. 125.
    Williams G, Pickup J, Clark A, Bowcock S, Cooke E, Keen H. Changes in blood flow close to subcutaneous insulin injection site in stable and brittle diabetics. Diabetes 1983; 32: 466–73.PubMedGoogle Scholar
  126. 126.
    Zingg W, Rappaport AM, Leibel BS. Studies on transhepatic absorption. Can J Physiol Pharmacol 1986; 64: 231–4.PubMedGoogle Scholar
  127. 127.
    Selam J-L, Bergman RN, Raccah D, Jean-Didier N, Lozano J, Charles MA. Determination of portal insulin absorption from peritoneum via novel nonisotopic method. Diabetes 1990; 39: 1361–5.PubMedGoogle Scholar
  128. 128.
    Ward BG, Mather SJ, Hawkins LR et al Localization of radioiodine conjugated to the monoclonal antibody HMFG2 in human ovarian carcinoma: assessment of intravenous and intraperitoneal routes of administration. Cancer Res 1987; 47: 4719–23.PubMedGoogle Scholar
  129. 129.
    Dedrick RL, Flessner MF. Pharmacokinetic Considerations on Monoclonal Antibodies. Immunity to Cancer. II. New York: Alan R. Liss, 1989, pp. 429–38.Google Scholar
  130. 130.
    Griffin TW, Collins J, Bokhari F et al Intraperitoneal immunoconjugates. Cancer Res 1990; 50: 1031–8s.Google Scholar
  131. 131.
    Clauss MA, Jain RK. Interstitial transport of rabbit and sheep antibodies in normal and neoplastic tissues. Cancer Res 1990; 50: 3487–92.PubMedGoogle Scholar
  132. 132.
    Flessner MF, Lofthouse J, Zakaria ER. In vivo diffusion of immunoglobulin G in muscle: effects of binding, solute exclusion, and lymphatic removal. Am J Physiol 1997; 273: H2783–93.PubMedGoogle Scholar
  133. 133.
    Berk DA, Yuan F, Leunig M, Jain RK. Direct in vivo measurement of targeted binding in a human tumor xenograft. Biophysisics 1997; 94: 1785–90.Google Scholar
  134. 134.
    Fujimori K, Covell DG, Fletcher JE, Weinstein JN. Modeling analysis of the global and microscopic distribution of immunoglobulin G, F(ab’)2, and Fab in tumors. Cancer Res 1989; 49: 5656–63.PubMedGoogle Scholar
  135. 135.
    Fujimori K, Covell DB, Fletcher JE, Weinstein JN. A modeling analysis of monoclonal antibody percolation through tumors: a binding-site barrier. J Nucl Med 1990; 31: 1191–8.PubMedGoogle Scholar
  136. 136.
    van Osdol W, Fujimori K, Weinstein JN. An analysis of monoclonal antibody distribution in microscopic tumor nodules: consequences of a `binding site barrier’. Cancer Res 1991; 51: 4776–84.PubMedGoogle Scholar
  137. 137.
    Flessner MF. Peritoneal transport physiology: insights from basic research. J Am Soc Nephrol 1991: 2: 122–35.PubMedGoogle Scholar
  138. 138.
    Flessner MF, Dedrick RL. Tissue-level transport mechanisms of intraperitoneally-administered monoclonal antibodies. J Controlled Rel 1998; 53: 69–75.Google Scholar
  139. 139.
    Rippe B, Haraldsson B. Fluid and protein fluxes across small and large pores in the microvasculature. Application of two-pore equations. Acta Physiol Scand 1987; 131: 411–28.PubMedGoogle Scholar
  140. 140.
    Flessner MF, Dedrick RL. Monoclonal antibody delivery to intraperitoneal tumors in rats: effects of route of adminstration and intraperitoneal solution osmolality. Cancer Res. 1994; 54: 4376–84.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2000

Authors and Affiliations

  • M. F. Flessner
  • R. L. Dedrick

There are no affiliations available

Personalised recommendations