The clinical pharmacology of methotrexate

Temporary Remissions in Acute Leukemia in Children Produced by Folic Acid Antagonist, 4-Aminopteroyl-Glutamic Acid (Aminopterin)

1948 • 1,702 citations

Methotrexate: Distribution in Cerebrospinal Fluid after Intravenous, Ventricular and Lumbar Injections

1975 • 676 citations

Adjuvant Methotrexate and Citrovorum-Factor Treatment of Osteogenic Sarcoma

1974 • 484 citations

Neurotoxicity of Commonly Used Antineoplastic Agents

1974 • 403 citations

Use of Plasma Pharmacokinetics to Predict and Prevent Methotrexate Toxicity

1977 • 390 citations

Specific Binding of 4-Amino Folic Acid Analogues by Folic Acid Reductase

1961 • 389 citations

Carrier-mediated Transport of the Folic Acid Analogue, Methotrexate, in the L1210 Leukemia Cell

1968 • 384 citations

Antimetabolite-metabolite combination cancer chemotherapy.Effects of intra-arterial methotrexate—intramuscular citrovorum factor therapy in human cancer

1959 • 319 citations

THE CHARACTERISTICS OF THE MEMBRANE TRANSPORT OF AMETHOPTERIN AND THE NATURALLY OCCURRING FOLATES

1971 • 291 citations

METHOTREXATE-INDUCED PNEUMONITIS

1976 • 276 citations

The effect of organic acids on renal clearance of methotrexate in man

1969 • 267 citations

7-Hydroxymethotrexate as a urinary metabolite in human subjects and rhesus monkeys receiving high dose methotrexate.

1976 • 256 citations

Threshold Methotrexate Concentration for In Vivo Inhibition of DNA Synthesis in Normal and Tumorous Target Tissues

1973 • 240 citations

The effects of prophylactic treatment of the central nervous system on the intellectual functioning of children with acute lymphocytic leukemia

1981 • 232 citations

The metabolic fate of tritiated methotrexate. II. Absorption and excretion in man.

1965 • 223 citations

Immunosuppressive and Cytotoxic Chemotherapy: Long-Term Complications

1975 • 214 citations

The Clinical Pharmacology of Antineoplastic Agents

1975 • 181 citations

Defective transport of amethopterin (methotrexate) as a mechanism of resistance to the antimetabolite in L5178Y leukemic cells

1962 • 172 citations

The reversal of methotrexate cytotoxicity to mouse bone marrow cells by leucovorin and nucleosides.

1976 • 163 citations

Pharmacokinetics of methotrexate

1974 • 158 citations

Drugs Five Years Later: Methotrexate

1977 • 153 citations

High dose methotrexate with leucovorin rescue

1980 • 153 citations

Improved therapeutic index of methotrexate with "leucovorin rescue".

1973 • 148 citations

Evidence for the cytotoxic activity of polyglutamate derivatives of methotrexate.

1980 • 147 citations

On the nature of a transport alteration determining resistance to amethopterin in the L1210 leukemia.

1968 • 129 citations

Pharmacokinetics of methotrexate

1973 • 125 citations

Effect of route of administration and effusions on methotrexate pharmacokinetics.

1974 • 124 citations

Weekly methotrexate-calcium leucovorin rescue: effect of alkalinization on nephrotoxicity; pharmacokinetics in the CNS; and use in CNS non-Hodgkin's lymphoma.

1977 • 117 citations

The Clinical Pharmacology of Antineoplastic Agents

1975 • 117 citations

Studies with a mathematical model of folate metabolism

1973 • 116 citations

A randomized prospective comparison of intermittent methotrexate, methotrexate with leucovorin, and a methotrexate combination in head and neck cancer

1981 • 112 citations

Methotrexate therapy of head and neck cancer: improvement in therapeutic index by the use of leucovorin "rescue".

1970 • 110 citations

The effect of photon irradiation on blood-brain barrier permeability to methotrexate in mice

1977 • 110 citations

Studies of the metabolism of methotrexate by intestinal flora—I

1972 • 108 citations

High-Dose Methotrexate With Folinic Acid in the Treatment of Advanced Non-Hodgkin Lymphoma Including CNS Involvement

1977 • 107 citations

Clinical Pharmacology of Antineoplastic Drugs

1979 • 107 citations

The role of 7-hydroxymethotrexate during methotrexate anti-cancer therapy

1980 • 106 citations

Methotrexate-resistant Chinese hamster ovary cells contain a dihydrofolate reductase with an altered affinity for methotrexate

1980 • 106 citations

Monitoring of Methotrexate Delivery in Patients with Malignant Brain Tumors After Osmotic Blood-Brain Barrier Disruption

1981 • 104 citations

Competitive protein binding assay for methotrexate.

1975 • 100 citations

High-volume intraperitoneal chemotherapy with methotrexate in patients with cancer.

1981 • 100 citations

Presence of 2,4‐diamino‐N¹⁰‐methylpteroic acid after high‐dose methotrexate

1979 • 98 citations

Characteristics of transport of 4-amino antifolates and folate compounds by two lines of L5178Y lymphoblasts, one with impaired transport of methotrexate.

1979 • 93 citations

Effect of pleural effusion on high‐dose methotrexate kinetics

1978 • 92 citations

The prevention of methotrexate toxicity by thymidine infusions in humans.

1977 • 91 citations

Cytogenetic effect of methotrexate on human cells in vivo

1979 • 90 citations

Continuous infusion of methotrexate in children with acute leukemia

1967 • 89 citations

CAN FOOD INFLUENCE THE ABSORPTION OF METHOTREXATE IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKÆMIA?

1980 • 89 citations

Synthesis of methotrexate polyglutamates in L1210 murine leukemia cells.

1977 • 86 citations

Differential synthesis of methotrexate polyglutamates in normal proliferative and neoplastic mouse tissues in vivo.

1981 • 84 citations

The reversal of methotrexate toxicity by thymidine with maintenance of antitumour effects

1975 • 84 citations

Characteristics of the Vincristine-induced Augmentation of Methotrexate Uptake in Ehrlich Ascites Tumor Cells

1973 • 82 citations

Role of thymidylate synthetase activity in development of methotrexate cytotoxicity.

1979 • 81 citations

Prolonged inhibition of DNA synthesis associated with the accumulation of methotrexate polyglutamates by cultured human cells.

1978 • 78 citations

Long-duration intracavitary infusion of methotrexate with systemic leucovorin protection in patients with malignant effusions.

1981 • 76 citations

Role of drug concentration, duration of exposure, and endogenous metabolites in determining methotrexate cytotoxicity.

1977 • 76 citations

The mechanism of action of methotrexate. I. Interaction with a low-affinity intracellular site required for maximum inhibition of deoxyribonucleic acid synthesis in L-cell mouse fibroblasts.

1974 • 74 citations

Methotrexate polyglutamate synthesis by cultured human breast cancer cells.

1980 • 70 citations

Gene Amplification and Drug Resistance

1980 • 69 citations

5-fluorouracil-methotrexate synergy: enhancement of 5-fluorodeoxyridylate binding to thymidylate synthase by dihydropteroylpolyglutamates.

1980 • 68 citations

Tissue culture studies on pleural effusions from breast carcinoma patients.

1974 • 67 citations

Enzymatic Cleavage of Methotrexate provides a Method for Prevention of Drug Toxicity

1972 • 67 citations

Thymidine rescue of high-dose methotrexate in humans.

1978 • 66 citations

High-dose methotrexate in acute lymphocytic leukemia.

1977 • 63 citations

A methotrexate insensitive variant of folate reductase present in two lines of methotrexate-resistant L5178Y cells

1980 • 61 citations

Formation of methotrexate polyglutamates in rat hepatocytes.

1979 • 58 citations

Accumulation of methotrexate diglutamate in human liver during methotrexate therapy

1977 • 57 citations

Methotrexate cytotoxicity in cultured human leukemic cells studied by flow cytometry.

1981 • 55 citations

Effects of sulfhydryl inhibitors upon transport of folate compounds into L1210 cells

1974 • 54 citations

The relative contribution of drug concentration and duration of exposure to mouse bone marrow toxicity during continuous methotrexate infusion.

1977 • 54 citations

Perturbation of Generation Cycle of Human Leukemic Myeloblasts In Vivo by Methotrexate

1971 • 54 citations

Kinetic model for the disposition and metabolism of moderate and high-dose methotrexate (NSC-740) in man.

1975 • 52 citations

The mechanism of action of methotrexate. III. Requirement of free intracellular methotrexate for maximal suppression of (14C)formate incorporation into nucleic acids and protein.

1975 • 52 citations

Dose-dependent metabolism of methotrexate in man and rhesus monkeys.

1977 • 51 citations

Methotrexate in the Treatment of Cancer

1961 • 51 citations

Methotrexate absorption in children with acute lymphoblastic leukemia.

1981 • 48 citations

Effect of oral prophylactic broad spectrum nonabsorbable antibiotics on the gastrointestinal absorption of nutrients and methotrexate in small cell bronchogenic carcinoma patients

1976 • 48 citations

Potentiation of the antitumor activity of methotrexate by concurrent infusion of thymidine.

1978 • 47 citations

Some observations on the human pharmacology of methotrexate.

1977 • 47 citations

Site of Action of Methotrexate in Psoriasis

1969 • 47 citations

High-pressure liquid chromatography analysis of methotrexate polyglutamates in cultured human breast cancer cells

1981 • 47 citations

Increased accumulation of methotrexate by murine tumor cells in vitro in the presence of probenecid which is mediated by a preferential inhibition of efflux.

1981 • 46 citations

Long-Term Remissions in Childhood Acute Leukemia

1966 • 46 citations

The protein binding of methotrexate by the serum of normal subjects

1979 • 43 citations

A pH-dependent, carrier-mediated transport system for the folate analog, amethopterin, in rat jejunum.

1977 • 43 citations

Analysis of the cytotoxic determinants for methotrexate (NSC 740): a role for 'free' intracellular drug

1975 • 42 citations

METHOTREXATE MENINGITIS

1972 • 40 citations

5-Methyltetrahydrofolate transport by hepatoma cells and methotrexate-resistant sublines in culture.

1981 • 38 citations

Enhancement of the therapeutic effectiveness of methotrexate and protection of normal proliferating tissues with purines and pyrimidines

1977 • 38 citations

Hemodialysis and enzymatic cleavage of methotrexate in man

1978 • 37 citations

Increased therapeutic index using moderate dose methotrexate and leucovorin twice weekly vs. weekly high dose methotrexate-leucovorin in patients with advanced squamous carcinoma of the head and neck: A safe new effective regimen

1981 • 36 citations

Unbalanced Deoxyribonucleotide Synthesis Caused by Methotrexate

1972 • 36 citations

Extracellular recovery of methotrexate-polyglutamates following efflux from L1210 leukemia cells

1980 • 35 citations

5-fluorouracil and methotrexate combination chemotherapy: The effect of drug scheduling

1981 • 35 citations

A clinical and pharmacological study of high-dose methotrexate with minimal leucovorin rescue.

1979 • 34 citations

Relative biochemical aspects of low and high doses of methotrexate in mice.

1977 • 33 citations

Pharmacokinetic considerations on resistance to anticancer drugs.

1975 • 33 citations

Thymidine requirements for the rescue of patients treated with high-dose methotrexate.

1980 • 33 citations

SCHEDULE-DEPENDENT SYNERGISM AND ANTAGONISM BETWEEN METHOTREXATE AND ASPARAGINASE

1975 • 32 citations

Enhancement of methotrexate absorption by subdivision of dose

1979 • 30 citations

Interaction of chemotherapeutic agents with methotrexate and 5-fluorouracil and its effect on de novo DNA synthesis.

1975 • 29 citations

Effect of methotrexate on 5-phosphoribosyl 1-pyrophosphate levels in L1210 leukemia cells in vitro.

1980 • 28 citations

Dose dependent methotrexate elimination following bolus intravenous injection

1980 • 28 citations

Some Observations on the Reversibility of Methotrexate Toxicity in Normal Proliferating Tissues2

1977 • 28 citations

Reversibility of high-affinity binding of methotrexate in L1210 murine leukemia cells.

1978 • 26 citations

Effects of allopurinol on the therapeutic efficacy of methotrexate.

1975 • 26 citations

Cytokinetic comparison of thymidine and leucovorin rescue of marrow in humans after exposure to high-dose methotrexate.

1979 • 26 citations

Renal clearance of methotrexate in man during high-dose oral and intravenous infusion therapy

1981 • 24 citations

Effects of 2,4-dinitrophenol and other metabolic inhibitors on the bidirectional carrier fluxes, net transport, and intracellular binding of methotrexate in Ehrlich ascites tumor cells.

1980 • 23 citations

Effects of methotrexate on cellular metabolism: some critical elements in the drug-cell interaction.

1977 • 23 citations

A colorimetric assay system for tetrahydrofolate dehydrogenase

1968 • 22 citations

Natural Resistance to Methotrexate in Human Melanomas

1980 • 22 citations

Enterotoxic effect of methotrexate: does it influence the drug's absorption in children with acute lymphoblastic leukaemia?

1981 • 21 citations

Bioavailability of methotrexate: Implications for clinical use

1979 • 20 citations

Progress report on high-dose methotrexate (NSC-740) with citrovorum rescue in the treatment of metastatic bone tumors.

1974 • 20 citations

Absorption of methotrexate under standardized conditions in children with acute lymphoblastic leukaemia

1980 • 20 citations

Refractory acute leukaemia in adults treated with sequential colaspase and high-dose methotrexate

1978 • 20 citations

Anaphylactic reaction to high-dose methotrexate.

1979 • 20 citations

Methotrexate revisited

1976 • 19 citations

Inhibition of dihydrofolate reductase by methotrexate: A new look at an old problem

1980 • 18 citations

Studies with high-dose methotrexate--historical background.

1978 • 17 citations

Methotrexate-induced Changes in the Levels of 1-β-d-Arabinofuranosylcytosine Triphosphate in L1210 Cells

1979 • 17 citations

The enhancement effect of irradiation by methotrexate. Report of three complications

1980 • 17 citations

Inhibition of methotrexate polyglutamate accumulation in cultured human cells.

1981 • 17 citations

Change in Transfer Rate of Methotrexate from Spinal Fluid to Plasma during Intrathecal Therapy in Children and Adults

1980 • 16 citations

Schedule-dependent synergism of methotrexate and vincristine against murine L1210 leukemia.

1979 • 15 citations

Activity of free and carrier-bound methotrexate against transport-deficient and high dihydrofolate dehydrogenase-containing methotrexate-resistant L1210 cells.

1981 • 15 citations

Effect of hydration on plasma-methotrexate levels.

1977 • 13 citations

Site of action of methotrexate in psoriasis

1969 • 13 citations

Phase I trial of high-dose methotrexate with modified citrovorum factor rescue.

1978 • 13 citations

Selection of wild-type revertants from methotrexate-resistant cells containing an altered dihydrofolate reductase

1980 • 11 citations

Rapid plasma clearance and reduced rate and extent of urinary elimination of parenterally administered methotrexate as a result of severe vomiting and diarrhoea

1980 • 11 citations

Achievement of long duration methotrexate exposure with concurrent low dose thymidine protection: Influence on methotrexate pharmacokinetics

1980 • 10 citations

Triamterene-induced elevation of dihydrofolate reductase activity in human leukocytes

1968 • 10 citations

Pharmacokinetics of methotrexate administered via the hepatic artery

1981 • 10 citations

Effect of gentamicin and irradiation on the toxicity of high-dose methotrexate in rats.

1980 • 8 citations

Gamma-ray-line astronomy

1980 • 7 citations

Antifolates: in vivo kinetic considerations.

1977 • 7 citations

Limited effectiveness of in vitro high-dose methotrexate and leucovorin to overcome resistance in L1210 leukemia cells with elevations of dihydrofolate reductase

1980 • 6 citations

The Pharmacokinetics of Cyclophosphamide in Man Following Treatment with Methotrexate

1976 • 3 citations

Psychology and Science

1950 • 2 citations

Antimetabolites in the central nervous system.

1977 • 1 citations

Cell Kinetic Factors, Single Drugs and Combination

1980 • 1 citations