Methotrexate bioavailability after oral and intramuscular administration in children

Teresi, Mary E.; Crom, William R.; Choi, Kyung Jun; Mirro, Joseph; Evans, William E.

doi:10.1016/s0022-3476(87)80025-2

Cited by 71 publications

(28 citation statements)

References 17 publications

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“…Pharmacokinetic parameters were estimated assuming a first-order two-compartment model, using a Bayesian estimation algorithm, as implemented in ADAPT II software (24). The prior distribution of model parameters was based on data from children who received HDMTX or LDMTX, as previously described (25,26). The area under the concentration versus time curve (AUC) from 0 to 48 h, before the first dose of leucovorin, was calculated by standard trapezoidal methods, and steady state plasma concentration of MTX (Cp ss ) was estimated using the fitted 24-h concentration for HDMTX, and as (Cp ss min ϩ Cp ss max)/2 for LDMTX.…”

Section: Methodsmentioning

confidence: 99%

Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. A rationale for high-dose methotrexate.

Masson¹,

Relling²,

Synold³

et al. 1996

J. Clin. Invest.

183

126

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Section: Methodsmentioning

confidence: 99%

Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. A rationale for high-dose methotrexate.

Masson¹,

Relling²,

Synold³

et al. 1996

J. Clin. Invest.

183

126

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“…Duncan et al (5) proposed that intestinal mucositis develops through three inter-linked stages of increasing epithelial dysfunction: the initial inflammatory phase, the epithelial degradation phase, and the ulceration/bacterial phase. Subsequently, there is a re-establishment of functional epithelial (16,22) . Recently, Miyazono et al (14) demonstrated that neutrophil infiltration and oxidative stress were involved in MTX-induced intestinal mucositis.…”

Section: Introductionmentioning

confidence: 99%

Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats

Soares

Lopes

Mota

et al. 2011

Arq. Gastroenterol.

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-Context -Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. Objectives -To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis. Methods -Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously) or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration). Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry. Results -After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment. Conclusion -Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats. HEADINGS -Mucositis. Methotrexate. Gastric emptying. Gastrointestinal transit. Rats.

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“…In addition, we note that the interpatient variability in oral pharmacokinetics (coefficient of variation = 34.7%; n = 26) is less than that which has been observed for methotrexate (up to 59%), at approximately equipotent doses (16,17,39).…”

Section: Discussionmentioning

confidence: 55%

Phase II Trial of Oral Aminopterin for Adults and Children with Refractory Acute Leukemia

Cole

Drachtman

Smith³

et al. 2005

Clinical Cancer Research

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Purpose:To determine the antileukemic activity of weekly oral aminopterin in patients with refractory acute leukemia; to describe the pharmacodynamic properties of aminopterin; and to contrast the intracellular metabolism of aminopterin and methotrexate by patients' blasts in vitro. Experimental Design: Forty-six patients were enrolled in three strata: children with acute lymphoblastic leukemia (ALL), adults with ALL, and patients with acute myeloid leukemia (AML). Aminopterin was given weekly, in two doses of 2 mg/m 2 ,12 hours apart. Limited sampling pharmacokinetic analysis was done during the first week of therapy. Accumulation of [ No relationship between aminopterin pharmacokinetics and response was seen. In vitro, aminopterin showed more consistent metabolism by leukemic blasts to polyglutamates than methotrexate. Lineage-specific differences in the pattern of intracellular antifolylpolyglutamates were observed. Conclusions: Weekly oral aminopterin has significant activity among children with refractory ALL.With greater cellular accumulation and metabolism, more reliable bioavailability than methotrexate, and tolerable toxicity at this dose and schedule, aminopterin deserves further study as a potent alternative to methotrexate.

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Methotrexate bioavailability after oral and intramuscular administration in children

Cited by 71 publications

References 17 publications

Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. A rationale for high-dose methotrexate.

Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. A rationale for high-dose methotrexate.

Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats

Phase II Trial of Oral Aminopterin for Adults and Children with Refractory Acute Leukemia

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