Pharmacokinetics of Low-Dose Methotrexate in Rheumatoid Arthritis Patients

Herman, Ronald A.; Veng‐Pedersen, Peter; Hoffman, John R.; Koehnke, R; Fürst, Daniel E.

doi:10.1002/jps.2600780219

Cited by 125 publications

(67 citation statements)

References 19 publications

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“…Absorption of oral doses of MTX shows considerable variation; even at moderate doses of 15-20 mg/week, absorption varies considerably between doses and individuals (19). The bioavailability of 10 mg/m 2 (ϳ17.5 mg), relative to intravenous administration, is reported to range from 0.25 to 1.49, with a mean of 0.70 (20). At higher doses, the intestinal folate transport system saturates and the parenteral route is required to achieve higher blood levels (19).…”

Section: Discussionmentioning

confidence: 99%

Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: A randomized, controlled trial

Lambert¹,

Sandhu²,

Lochhead³

et al. 2004

Arthritis & Rheumatism

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Results. Sixty-four patients were eligible for entry and were switched from oral MTX to 15 mg/week IM MTX. At baseline, the mean ؎ SD DAS28 was 5.6 ؎ 0.88; after 6 weeks of IM MTX, the DAS28 had improved by a mean of 0.42 (95% confidence interval [95% CI] 0.15-0.69). At 6 weeks, 54 patients still had a DAS28 of >3.2 and were therefore eligible for randomization. By 22 weeks, 1 patient (3.7%) in each group achieved the primary outcome of a DAS28 <3.2 (95% CI for the difference between the groups ؊15% to ؉15%). Five patients (18.5%) in each group showed an improvement of >1.2 in the DAS28 (95% CI for the difference between the groups ؊18% to ؉18%). One patient (3.7%) in each group achieved an ACR20 response, but none achieved a good response as defined by the EULAR response criteria. One patient in each group had a serious adverse reaction; minor adverse reactions were more frequently reported in the dose escalation group.Conclusion. Switching from oral to parenteral MTX 15 mg/week results in a minor improvement in disease control. For patients with active RA receiving 15

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Section: Discussionmentioning

confidence: 99%

Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: A randomized, controlled trial

Lambert¹,

Sandhu²,

Lochhead³

et al. 2004

Arthritis & Rheumatism

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“…Although the kinetics of MTX following high doses for the treatment of neoplastic disease have been studied extensively, studies of intermittent low-dose MTX treatment have been restricted to the first 24 h after dosing and plasma drug concentrations throughout the dosage interval have not been reported (Balis et al, 1983;Christophidis et al, 1979;Edelman et al, 1984;Evans et al, 1982;Furst et al, 1986;Herman et al, 1989;Pearson et al, 1987;Shen & Azarnoff, 1978;Sinett et al, 1989;Teresi et al, 1989;Wang & Fujimoto, 1984). In most of the reported studies MTX was measured by immunological assay and consequently plasma concentrations of 7-OHMTX could not be determined.…”

Section: Introductionmentioning

confidence: 99%

The pharmacokinetics of methotrexate and its 7‐hydroxy metabolite in patients with rheumatoid arthritis.

Seideman

Beck

Eksborg

et al. 1993

Brit J Clinical Pharma

107

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“…As part of an ongoing clinical study of lowdose MTX in RA, he participated in initial pharmacokinetic investigations of MTX (8) Blood samples were initially collected as follows: at baseline (before MTX dose). at 15 minutes after administration, then every hour for 8 hours, every 4 hours for 28 hours, and every 12 hours for 60 hours.…”

Section: Patient and Methodsmentioning

confidence: 99%

“…AU other chemicals and reagents, including analytical standards, were of grade A quality. The assay used to quantitate MTX before surgery was a radiochemical ligand-binding assay described previously (8). The 2 major metabolites of MTX, 7-hydroxymethotrexate (7-OH-MTX) and 2,4-diamin0-N'~-methylpteroic acid (APA), showed no cross-reactivity.…”

Section: Patient and Methodsmentioning

confidence: 99%

Biliary elimination of low‐dose methotrexate in humans

Nuernberg

Koehnke

Solsky

et al. 1990

Arthritis & Rheumatism

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We studied the pharmacokinetics of methotrexate (MTX) in a 64-year-old man with rheumatoid arthritis. After 6 months of treatment, acute clinical complications arose, requiring emergency laparotomy and cholecystotomy. A biliary tube was inserted, and this allowed for direct analysis of the bile. The pharmacokmetics of 2 separate doses of MTX (orally and intravenously) were assessed (dosage 10 mg/m2). No substantive differences in the pharmacokinetics were found between pre-and post-cholecystotomy MTX treatment, including clearance rates, volumes of distribution, and terminal half-lives. The results, however, demonstrated a change in the bioavailability of the drug (decreasing from 84.7% to 38.9%). Based on extrapolations of the data, with assumed rates of bile flow, the findings also suggest that there is substantial biliary Presented in part at the 2 n d Annual Meeting of the American Rheumatism Association. Houston, TX. May 1988.

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Pharmacokinetics of Low-Dose Methotrexate in Rheumatoid Arthritis Patients

Cited by 125 publications

References 19 publications

Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: A randomized, controlled trial

Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: A randomized, controlled trial

The pharmacokinetics of methotrexate and its 7‐hydroxy metabolite in patients with rheumatoid arthritis.

Biliary elimination of low‐dose methotrexate in humans

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