Methotrexate (MTX) is a folate analog competitive with reduced folates for cellular transport and metabolism. Since the normal plasma folate concentration is only 10(-8) M, we tested the possibility that there may be a saturable uptake of MTX by proliferating tumor tissue at plasma MTX concentrations of only 10(-7) to 10(-6) M. Patients with advanced malignancies, refractory to accepted therapy, were given low-dose oral MTX (30-60 mg/m2 total dose in four to eight divided doses). Tumor tissue was biopsied 18-24 h after the last oral dose of MTX. The concentrations of MTX and its polyglutamated derivatives were measured in these samples. Forty-eight percent of the drug in the tumor samples was present as a polyglutamated derivative.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/BF00252965 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Comprehensive Parent-Metabolite PBPK/PD Modeling Insights Into Methotrexate Personalized Dosing Strategies in Patients With Rheumatoid Arthritis.
CPT Pharmacometrics Syst Pharmacol
January 2025
Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Rheumatoid arthritis (RA) is a major public health concern, which can cause serious outcomes. Low-dose methotrexate (MTX) is a cornerstone in RA treatment, but there is significant heterogeneity in clinical response. To evaluate underlying sources of pharmacokinetic variability and clinical response of MTX, a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed using PK-sim and Mobi (version 11.
View Article and Find Full Text PDFPredictors of treatment failure of tubal pregnancy with single-dose methotrexate regimen - a systematic review and meta-analysis.
J Obstet Gynaecol
December 2025
Department of Obstetrics and Gynecology, the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.
Background: Ectopic pregnancies represent a potentially life-threatening medical emergency, with 95% being tubal. This meta-analysis aimed to identify early predictors for single-dose methotrexate (MTX) treatment failure in tubal pregnancies.
Methods: A literature search was conducted across several databases from their inception to December 2023, with references in the selected studies manually reviewed.
Inhibition of Growth and Lung Metastasis of Breast Cancer by pH-Responsive Methotrexate/Curcumin-Loaded Chitosan-Stabilized Nanoemulsions.
Pharm Dev Technol
January 2025
Department of Psychiatry and Behavioral Sciences, Department of Pharmacology, School of Medicine, University of Washington, Seattle, WA, USA.
Chemotherapeutic agents are widely used to combat breast cancer. However, due to their non-selective biodistribution, their usage is associated with severe adverse effects on healthy tissues. In this study, a chitosan-stabilized nanoemulsion (CSNE) was prepared for the codelivery of curcumin (CUR) and methotrexate (MTX).
View Article and Find Full Text PDFApplication of Microsponge Drug Platform to Enhance Methotrexate Administration in Rheumatoid Arthritis Therapy.
Pharmaceutics
December 2024
Nanofaber S.r.l., Via Anguillarese 301, 00123 Rome, Italy.
Background/objectives: This study aimed to develop a novel nanotechnological slow-release drug delivery platform based on hyaluronic acid Microsponge (MSP) for the subcutaneous administration of methotrexate (MTX) in the treatment of rheumatoid arthritis (RA). RA is a chronic autoimmune disease characterized by joint inflammation and damage, while MTX is a common disease-modifying antirheumatic drug (DMARD), the conventional use of which is limited by adverse effects and the lack of release control.
Methods: MSP were synthesized as freeze-dried powder to increase their stability and allow for a facile reconstitution prior to administration and precise MTX dosing.
Pharmacogenetics of Neoadjuvant MAP Chemotherapy in Localized Osteosarcoma: A Study Based on Data from the GEIS-33 Protocol.
Pharmaceutics
December 2024
Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain.
Osteosarcoma is a rare disease, but it is the most frequent malignant bone tumor. Primary treatment consists of preoperative MAP (methotrexate (MTX), doxorubicin and cisplatin) chemotherapy followed by surgery and adjuvant chemotherapy. Pathological response to preoperative chemotherapy is one of the most important prognostic factors, but molecular biomarkers are lacking.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!