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Pharmacologic Studies of Methotrexate in Cancer Patients With Uropathy

Pharmacologic Studies of Methotrexate in Cancer Patients With Uropathy Abstract Methotrexate (4-amino-N10-methylpteroylglutamic acid) is well tolerated by most patients using the usual dosage schedules and routes of administration (oral, intravenous, and intramuscular), as previously described by Farber et al,1 Burchenal et al,2 Schoenbach et al,3 and others. Moreover, more recent studies of the clinical effects of methotrexate when given by several dose schedules and routes of administration (ie, continuous intravenous and intra-arterial infusion, intrathecal and intraventricular injections) have shown that this antimetabolite is well tolerated to the extent of acceptable toxicity.4-8 We have previously reported the clinical effects of the protracted administration of methotrexate,9 the general pharmacodynamics in the human,10 and studies of methotrexate in the human central nervous system.11 A total of 259 patients was included in these clinical pharmacologic investigations. During these studies it became apparent that in patients with impaired renal function, the methotrexate serum levels and urinary References 1. Farber, S., et al: Temporary Remissions in Acute Leukemia in Children Produced by Folic Acid Antagonist, 4-Aminopteroyglutamic Acid (Aminopterin) , New Eng J Med 238:787-793 ( (June 3) ) 1948.Crossref 2. Burchenal, J.H., et al: Effects of Folic Acid Antagonists and 2,6-Diaminopurine on Neoplastic Disease: With Special Reference to Acute Leukemia , Cancer 4:549-569 ( (May) ) 1951.Crossref 3. Schoenbach, E.B.; Colsky, J.; and Greenspan, E.M.: Observations on Effects of Folic Acid Antagonists, Aminopterin and Amethopterin, in Patients With Advanced Neoplasms , Cancer 5:1201-1220 ( (Nov) ) 1952.Crossref 4. Sullivan, R.D., et al: Clinical Effects of the Continuous Intravenous and Intra-Arterial Infusion of Cancer Chemotherapeutic Compounds , Cancer Chemother Rep 16:499-510 ( (Feb) ) 1962. 5. Sullivan, R.D.; Miller, E.; and Sykes, M.P.: Antimetabolite-Methotrexate Combination Cancer Chemotherapy; Effects of Intra-Arterial Methotrexate-Intramuscular Citrovorum Factor Therapy in Human Cancer , Cancer 12:1248-1262 ( (Nov) -Dec) 1959.Crossref 6. Rubin, R.C., et al: Cerebrospinal Fluid Perfusion for Central Nervous System Neoplasms , Neurology 16:680-692 ( (July) ) 1966.Crossref 7. Newton, W.A., Jr., and Sayers, M.P.: Intrathecal Methotrexate Therapy of Brain Tumors of Childhood , Proc Amer Assoc Cancer Res 6:48 ( (March) ) 1965. 8. Whiteside, J.A., et al: Intrathecal Amethopterin in Neurological Manifestation of Leukemia , Arch Intern Med 101:279-285 ( (Feb) ) 1958.Crossref 9. Sullivan, R.D., et al: Re-evaluation of Methotrexate as an Anticancer Drug , Surg Gynec Obstet 125:819-824 ( (Oct) ) 1967. 10. Zurek, W.Z., et al: Pharmacologic Studies of Methotrexate in Man , Surg Gynec Obstet 126:331-338 ( (Feb) ) 1968. 11. Ojima, Y., and Sullivan, R.D.: Pharmacology of Methotrexate in the Human Central Nervous System , Surg Gynec Obstet 125:1035-1040 ( (Nov) ) 1967. 12. Liguori, V.R., et al: Effects of Different Dose Schedules of Amethopterin on Serum and Tissue Concentrations and Urinary Excretion Patterns , Clin Pharmacol Ther 3:34-40 ( (Jan) -Feb) 1962. 13. Sullivan, R.D.: " Dose, Duration, and Route of Administration Studies of Methotrexate in Clinical Cancer Chemotherapy ," in Porter, R., and Wiltshaw, E. (eds.): Methotrexate in the Treatment of Cancer , Bristol, England: John Wright & Sons, Ltd., Medical Publishers, 1962, pp 50-55. 14. Burchenal, J.H., et al: A Simple Method for Determination of Levels of Amethopterin in Blood and Urine , Proc Soc Exp Biol Med 78:603-606 ( (Nov) ) 1951.Crossref 15. Rubin, R.C., et al: Uptake of Methotrexate-3H by Rabbit Kidney Slices , Cancer Res 27:553-557 ( (March) ) 1967. 16. Henderson, E.S., and Francis, F.: Renal Clearance of Methotrexate-3H in Man , Clin Res 12:285 ( (April) ) 1964. 17. Methotrexate in the Treatment of Cancer, Symposium , Brit Med J 2:954-955 ( (Oct 7) ) 1961.Crossref 18. Werkheiser, W.C.: Specific Binding of 4-Aminofolic Acid Analogues by Folic Acid Reductase , J Biol Chem 236:888-893 ( (March) ) 1961. 19. Werkheiser, W.C.: The Relation of Folic Acid Reductase to Aminopterin Toxicity , J Pharmacol Exp Ther 137:167-172 ( (Aug) ) 1962. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Pharmacologic Studies of Methotrexate in Cancer Patients With Uropathy

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Publisher
American Medical Association
Copyright
Copyright © 1970 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1970.01340200061014
Publisher site
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Abstract

Abstract Methotrexate (4-amino-N10-methylpteroylglutamic acid) is well tolerated by most patients using the usual dosage schedules and routes of administration (oral, intravenous, and intramuscular), as previously described by Farber et al,1 Burchenal et al,2 Schoenbach et al,3 and others. Moreover, more recent studies of the clinical effects of methotrexate when given by several dose schedules and routes of administration (ie, continuous intravenous and intra-arterial infusion, intrathecal and intraventricular injections) have shown that this antimetabolite is well tolerated to the extent of acceptable toxicity.4-8 We have previously reported the clinical effects of the protracted administration of methotrexate,9 the general pharmacodynamics in the human,10 and studies of methotrexate in the human central nervous system.11 A total of 259 patients was included in these clinical pharmacologic investigations. During these studies it became apparent that in patients with impaired renal function, the methotrexate serum levels and urinary References 1. Farber, S., et al: Temporary Remissions in Acute Leukemia in Children Produced by Folic Acid Antagonist, 4-Aminopteroyglutamic Acid (Aminopterin) , New Eng J Med 238:787-793 ( (June 3) ) 1948.Crossref 2. Burchenal, J.H., et al: Effects of Folic Acid Antagonists and 2,6-Diaminopurine on Neoplastic Disease: With Special Reference to Acute Leukemia , Cancer 4:549-569 ( (May) ) 1951.Crossref 3. Schoenbach, E.B.; Colsky, J.; and Greenspan, E.M.: Observations on Effects of Folic Acid Antagonists, Aminopterin and Amethopterin, in Patients With Advanced Neoplasms , Cancer 5:1201-1220 ( (Nov) ) 1952.Crossref 4. Sullivan, R.D., et al: Clinical Effects of the Continuous Intravenous and Intra-Arterial Infusion of Cancer Chemotherapeutic Compounds , Cancer Chemother Rep 16:499-510 ( (Feb) ) 1962. 5. Sullivan, R.D.; Miller, E.; and Sykes, M.P.: Antimetabolite-Methotrexate Combination Cancer Chemotherapy; Effects of Intra-Arterial Methotrexate-Intramuscular Citrovorum Factor Therapy in Human Cancer , Cancer 12:1248-1262 ( (Nov) -Dec) 1959.Crossref 6. Rubin, R.C., et al: Cerebrospinal Fluid Perfusion for Central Nervous System Neoplasms , Neurology 16:680-692 ( (July) ) 1966.Crossref 7. Newton, W.A., Jr., and Sayers, M.P.: Intrathecal Methotrexate Therapy of Brain Tumors of Childhood , Proc Amer Assoc Cancer Res 6:48 ( (March) ) 1965. 8. Whiteside, J.A., et al: Intrathecal Amethopterin in Neurological Manifestation of Leukemia , Arch Intern Med 101:279-285 ( (Feb) ) 1958.Crossref 9. Sullivan, R.D., et al: Re-evaluation of Methotrexate as an Anticancer Drug , Surg Gynec Obstet 125:819-824 ( (Oct) ) 1967. 10. Zurek, W.Z., et al: Pharmacologic Studies of Methotrexate in Man , Surg Gynec Obstet 126:331-338 ( (Feb) ) 1968. 11. Ojima, Y., and Sullivan, R.D.: Pharmacology of Methotrexate in the Human Central Nervous System , Surg Gynec Obstet 125:1035-1040 ( (Nov) ) 1967. 12. Liguori, V.R., et al: Effects of Different Dose Schedules of Amethopterin on Serum and Tissue Concentrations and Urinary Excretion Patterns , Clin Pharmacol Ther 3:34-40 ( (Jan) -Feb) 1962. 13. Sullivan, R.D.: " Dose, Duration, and Route of Administration Studies of Methotrexate in Clinical Cancer Chemotherapy ," in Porter, R., and Wiltshaw, E. (eds.): Methotrexate in the Treatment of Cancer , Bristol, England: John Wright & Sons, Ltd., Medical Publishers, 1962, pp 50-55. 14. Burchenal, J.H., et al: A Simple Method for Determination of Levels of Amethopterin in Blood and Urine , Proc Soc Exp Biol Med 78:603-606 ( (Nov) ) 1951.Crossref 15. Rubin, R.C., et al: Uptake of Methotrexate-3H by Rabbit Kidney Slices , Cancer Res 27:553-557 ( (March) ) 1967. 16. Henderson, E.S., and Francis, F.: Renal Clearance of Methotrexate-3H in Man , Clin Res 12:285 ( (April) ) 1964. 17. Methotrexate in the Treatment of Cancer, Symposium , Brit Med J 2:954-955 ( (Oct 7) ) 1961.Crossref 18. Werkheiser, W.C.: Specific Binding of 4-Aminofolic Acid Analogues by Folic Acid Reductase , J Biol Chem 236:888-893 ( (March) ) 1961. 19. Werkheiser, W.C.: The Relation of Folic Acid Reductase to Aminopterin Toxicity , J Pharmacol Exp Ther 137:167-172 ( (Aug) ) 1962.

Journal

Archives of SurgeryAmerican Medical Association

Published: Feb 1, 1970

References