The pharmacology of methotrexate

Olsen, Elise A.

doi:10.1016/0190-9622(91)70199-c

Cited by 158 publications

(123 citation statements)

References 66 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…However, the mechanisms underlying the circadian rhythm have not been fully investigated. Espe cially, the relationship between the circadian rhythms of MTX cytotoxic activity and DNA synthesis is not clear, although MTX is considered to kill cells in the S phase by means of its irreversible binding to the enzyme dihydro folate reductase (DHFR) (6,7).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Chronotoxicity of Methotrexate in Mice and Its Relation to Circadian Rhythm of DNA Synthesis and Pharmacokinetics

Ohdo

Inoue

Yukawa

et al. 1997

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-The mechanisms underlying the circadian rhythm of methotrexate (MTX)-induced toxicity (body weight loss and leukopenia) were investigated from the viewpoints of the sensitivity of living organ isms to the drug and the pharmacokinetics of the drug. ICR male mice were housed in a standardized light-dark cycle (lights on at 0700, off at 1900) with food and water ad libitum. The body weight loss after an intraperitoneal injection of MTX (400 mg/kg) was more serious in the late dark period and the early light period and milder in the late light period and the early dark period. The MTX-induced leukopenia was more serious in the late dark period and the light period and milder in the early dark period. Lower toxicity was observed when DNA synthesis, dihydrofolate reductase (DHFR) activity in bone marrow cells and folate level in plasma decreased, and higher toxicity was observed when they increased. There was a significant circadian rhythm in plasma MTX concentration, with a higher level in the light period and a lower level in the dark period. The circadian rhythm of plasma MTX concentration was associated with that of MTX induced toxicity. The present study suggests that the circadian rhythm of MTX-induced toxicity is caused by that of the sensitivity of living organisms to the drug and the pharmacokinetics of the drug.

show abstract

mentioning

confidence: 99%

“…Methotrexate (MTX) is one of the most potent anti cancer agents, particularly for human leukemia, severe psoriasis and some solid tumors (6,7). The dose and du ration of treatment have been severely limited by the tox icity of the drug, which ranges from the unpleasant to the fatal.…”

mentioning

confidence: 99%

Chronotoxicity of Methotrexate in Mice and Its Relation to Circadian Rhythm of DNA Synthesis and Pharmacokinetics

Ohdo

Inoue

Yukawa

et al. 1997

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…Moreover, side effects of MTX high dose (MTX-HD) may be life-threatening; however, those of various doses of oral MTX are variable because of the interindividual variability of gastrointestinal absorption of this drug. Bone marrow, gastrointestinal mucosa and hair are particularly vulnerable to the effects of MTX, secondary to their high rate of cellular turnover, and because MTX concentration is inversely proportional to renal clearance [99], renal toxicity is frequent with MTX-HD.…”

Section: Medical Managementmentioning

confidence: 99%

Ectopic Pregnancy: Diagnosis, Prevention and Management

Abdulkareem¹,

Eidan²

2017

Obstetrics

View full text Add to dashboard Cite

An ectopic pregnancy (EP) falls within the area of the gynecological emergency and/or reproductive management of women, which is the implantation of fertilized ovum outside the endometrial cavity. The etiology of EP concentrated mainly on factor causes delayed transport of the fertilized ovum through the fallopian tube (favors implantation in tubal mucosa), thus giving rise to EP. This chapter describes the causes, diagnosis, prevention and the guidelines to improve the management of women who may have an EP, a major gynecological emergency that is a cause of morbidity or even mortality of women in first trimester. Three types of EP are diagnosed: tubal, cervical and ovarian; tubal is the main type. Identification of the signs and symptoms of acute and chronic EP in women, involving classical clinical trials or other symptoms common to early pregnancy, as well as evaluating the most important congenital and acquired factors related with EP, were discussed. Explanation of the most accurate methods used to diagnose the pregnancy including serum beta hCG and progesterone levels, medical history, ultrasonography, pregnancy tests and laparoscopy was also clarified. The evaluation of the most effective management tools of EP, including methotrexate administration and surgery (laparotomy and laparoscopy), was obviously explained.

show abstract

“…Hepatotoxicity is a common complication of long term treatment with MTX [15,16], especially in the case of obesity, alcoholism, diabetes, non-alcoholic steatohepatitis and hepatitis B or C infection [17,18]. Elevated aminotransferases level is the most common laboratory sign of hepatotoxicity.…”

Section: Hepatotoxicitymentioning

confidence: 99%

“…However the serum creatinine may be a misleading measure of renal function in older patients because of an overall reduction in lean muscle mass. Urine alkalinisation and leucoverin rescue are the cornerstones of the management of the earlier signs of renal dysfunction [15,27].…”

Section: Renal Toxicitymentioning

confidence: 99%

The Hematologic Toxicity of Methotrexate in Patients with Autoimmune Disorders

Rajnics¹,

Kellner²,

Kellner³

et al. 2017

J Neoplasm

View full text Add to dashboard Cite

The incidence of auto-immune diseases is increasing nowa-days. Despite of the development of diagnosis and management of diseases, they remained chronic diseases. The patient's lifespan expansion requires long-term treatment with harmful agents, such as Methotrexate or other immuno-suppressive drugs. The Methotrexate toxicities are based on the duration and cumulative dosing of drug, and the combination with other drugs. Myelosuppression and consequent pancytopenia is the most frequent hematologic toxicity, which occur mostly later during low dose methotrexate administration.We demonstrate three cases of low dose Methotrexate toxicity in older patients with rheumatoid arthritis and psoriasis.All patients were treated with low dose Methotrexate along more than one year continuously.Two old patients with RA and another with psoriasis developed pancytopenia causing severe neutropenia, cutaneous bleeding, and bruising and septic condition. They required intravenous antibiotic therapy, corticosteroids and limited transfusion dependence as a result of low dose Methotrexate.We have assessed the possible causes of Methotrexate toxicities and found that all patients used non-steroid anti-inflammatory drugs because of pain and protonpump inhibitor to avoid development of peptic ulcer. Two patients recovered, another died in septic condition.We would like to drawn attention of hematologists, dermatologists and rheumatologists to the harmful effect of low dose methotrexate in this patient population and emphasize the role of rigorous and consequent hematologic testing to avoid these severe late complications.

show abstract

The pharmacology of methotrexate

Cited by 158 publications

References 66 publications

Chronotoxicity of Methotrexate in Mice and Its Relation to Circadian Rhythm of DNA Synthesis and Pharmacokinetics

Chronotoxicity of Methotrexate in Mice and Its Relation to Circadian Rhythm of DNA Synthesis and Pharmacokinetics

Ectopic Pregnancy: Diagnosis, Prevention and Management

The Hematologic Toxicity of Methotrexate in Patients with Autoimmune Disorders

Contact Info

Product

Resources

About