Low-dose methotrexate in rheumatic diseases—Efficacy, side effects, and risk factors for side effects

Schnabel, A; Gross, Wolfgang L.

doi:10.1016/0049-0172(94)90027-2

Cited by 109 publications

(66 citation statements)

References 98 publications

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“…In dogs, DPC 333 administered orally at 1.7 mg/kg 15 min before the intravenous administration of [ MTX, a bicarboxylic acid (Fig. 1) structurally similar to folic acid, has been used for the treatment of rheumatoid arthritis at low doses (Weinblatt et al, 1985;Schnabel and Gross, 1994). MTX is minimally metabolized to 7-hydroxy MTX in vivo, whereas most MTX is eliminated as intact drug via renal and biliary excretion in humans (Henderson et al, 1965b;Lui et al, 1985;Nuernberg et al, 1990;Seideman et al, 1993;Chladek et al, 1998), and in the preclinical species including mice, rats, dogs, and monkeys (Henderson et al, 1965a;Steinberg et al, 1982;Masuda et al, 1997).…”

Section: Abstract: Dpc 333 [(2r)-2-{(3r)-3-amino-3-[4-(2-methylquinolmentioning

confidence: 99%

Effect of DPC 333 [(2R)-2-{(3R)-3-Amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide], a Human Tumor Necrosis Factor α-Converting Enzyme Inhibitor, on the Disposition of Methotrexate: A Transporter-Based Drug-Drug Interaction Case Study

Luo

Garner

Xiong³

et al. 2007

Drug Metab Dispos

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DPC 333 [(2R)-2-{(3R)-3-amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide]is a potent human tumor necrosis factor ␣-converting enzyme inhibitor with potential therapeutic implications for rheumatoid arthritis. Methotrexate (MTX), a drug for the treatment of rheumatoid arthritis, is eliminated primarily unchanged via renal and biliary excretion in humans as well as in rats and dogs. The objective of the present study was to investigate the potential effect of DPC 333 on the disposition of MTX. In dogs, DPC 333 administered orally at 1.7 mg/kg 15 min before the intravenous administration of [ MTX, a bicarboxylic acid (Fig. 1) structurally similar to folic acid, has been used for the treatment of rheumatoid arthritis at low doses (Weinblatt et al., 1985;Schnabel and Gross, 1994). MTX is minimally metabolized to 7-hydroxy MTX in vivo, whereas most MTX is eliminated as intact drug via renal and biliary excretion in humans (Henderson et al., 1965b;Lui et al., 1985;Nuernberg et al., 1990;Seideman et al., 1993;Chladek et al., 1998), and in the preclinical species including mice, rats, dogs, and monkeys (Henderson et al., 1965a;Steinberg et al., 1982;Masuda et al., 1997). In mice and rats, the routes of biliary and renal elimination contribute almost equally to the total body clearance of MTX, but in monkeys and humans, renal elimination is more extensive than biliary excretion (Henderson et al., 1965a,b;Steinberg et al., 1982;Williams and Huang, 1982;Nuernberg et al., 1990;Masuda et al., 1997). For example, after intravenous administration, the cumulative biliary excretion of MTX was 44 to 72% of the dose in bile duct-cannulated rats, but only 16% in rhesus monkeys with bile fistula; after intraperitoneal or intravenous administration, MTX recovery in feces was 45% of the dose in rats and 40% in mice, but only 13% in monkeys and 10% in humans. Biliary H.X. and K.L.R.B. were funded in part by Grant R01 GM41935 from the National Institutes of Health.Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

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Section: Abstract: Dpc 333 [(2r)-2-{(3r)-3-amino-3-[4-(2-methylquinolmentioning

confidence: 99%

Effect of DPC 333 [(2R)-2-{(3R)-3-Amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide], a Human Tumor Necrosis Factor α-Converting Enzyme Inhibitor, on the Disposition of Methotrexate: A Transporter-Based Drug-Drug Interaction Case Study

Luo

Garner

Xiong³

et al. 2007

Drug Metab Dispos

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“…Furthermore, TRAIL was found to have a negligible effect on blockage of inflammatory cytokine responses caused by a severe immunosuppression. This implies that TRAILbased RA therapy is probably free of immunosuppressionassociated side effects, which have been associated with other immunosuppressants examined in the context of RA (Schnabel and Gross, 1994;Borchers et al, 2004;Li et al, 2004).…”

mentioning

confidence: 99%

Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand on the Reduction of Joint Inflammation in Experimental Rheumatoid Arthritis

Jin

Chae²,

Kim³

et al. 2009

J Pharmacol Exp Ther

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This study focused on the potential therapeutic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on collagen-induced arthritis (CIA) and on the elucidation of the mechanisms involved. DBA/1J mice with established CIA were treated with various amount of recombinant soluble human TRAIL. The effects of TRAIL on the development and severity of CIA in this DBA/1J mouse model were assessed clinically and histologically, and a detailed investigation was conducted on proinflammatory cytokine and anticollagen-specific antibody levels. Cellular immunity was evaluated by investigating the proliferative responses and cytokine release profiles of splenocytes after TRAIL treatment. TRAIL treatment significantly reduced the severity and incidence of CIA, joint swelling, erythema, and edema. Histologic evaluations revealed that inflammatory cell infiltration, cartilage destruction, and bone erosion were significantly reduced in joints of TRAIL-treated mice with dose-dependent manner. TRAIL treatment also strongly decreased and/or normalized the productions of proinflammatory cytokines and of anti-collagen-specific antibodies in the sera of CIA mice. Furthermore, in vitro studies with primary splenocytes showed the cytotoxic effect of TRAIL on activated lymphocytes, with reduction of inflammatory cytokine release. These findings show that TRAIL administration is an effective anti-inflammatory treatment that prevents the development and progression of CIA in DBA/1J mice, and they suggest that TRAIL might be considered a potential treatment for human RA.

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“…In the present study, we investigated lung volumes and gas exchange prospectively in a cohort of patients with RA with the following aims: (1) to determine the incidence of pulmonary complications requiring MTX withdrawal, (2) to assess pulmonary function over time and (3) to search for risk factors for a loss of pulmonary function.…”

mentioning

confidence: 99%

“…LOW-DOSE weekly methotrexate (MTX) is increasingly used in the treatment of rheumatoid arthritis (RA) [1][2][3]. MTX has a favourable efficacy to toxicity profile over short and intermediate periods compared with other disease-modifying anti-rheumatic drugs (DMARDs) [4].…”

mentioning

confidence: 99%

Pulmonary Function in Rheumatoid Arthritis Treated With Low-Dose Methotrexate: A Longitudinal Study

et al. 1996

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SUMMARYLung volumes and gas exchange were investigated prospectively in 96 patients with rheumatoid arthritis selected without regard to pulmonary disorders and treated with i.m. methotrexate (MTX) injections [mean weekly dose 13.0 mg (5th-95th percentile (5-95 PC) 7.6-20.8)]. Individual changes over time during MTX treatment [mean duration 2.9 yr (5-95 PC 0.4-5.3)] were assessed by regression analyses in each individual. Forced vital capacity (FVQ remained stable in the majority of patients [mean annual change +0.8% (5-95 PC -8.1 to +14.0) of calculated normal value]. In addition, transfer factor using the indicator gas CO (Tuco) was unaltered in most patients [mean annual change -2.1% (5-95 PC -16.2 to +11.8) of predicted value]. However, there were significant decreases in the forced expiratory volume in 1 s (FEV,) before and after inhalation of 0.2 mg salbutamol [mean annual change -0.8% (5-95 PC -8.4 to +3.2) and -1.3% (5-95 PC -7.8 to +3.9) of the FVC measured, respectively]. In addition, there were significant increases in alveolar-arterial Po, gradients (P(A-.W)J) at rest and after exercise [mean annual change +1.7 mmHg (5-95 PC -5.2 to +12.2) and +1.8 mmHg (5-95 PC -3.5 to 9.0), respectively]. Nevertheless, the amounts were small in view of the reliability of the methods applied and reflect, at least in part, the normal process of ageing. The annual change in FEVi/FVC was negatively correlated with FEV,/FVC at baseline (R, = -0.46, P < 0.001). The annual change in T U co was also negatively correlated with Ti^o at baseline (Rs = -0.31, P = 0.028). No other risk factors for deterioration of lung volumes or gas exchange were found, including mean weekly MTX dose, age, gender, smoking, presence of rheumatoid factor and pulmonary function at baseline. We conclude that MTX has no major effect on pulmonary function in the majority of patients and that there is no evidence that patients with pre-existing pulmonary disease are at increased risk for further deterioration of lung function.

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Low-dose methotrexate in rheumatic diseases—Efficacy, side effects, and risk factors for side effects

Cited by 109 publications

References 98 publications

Effect of DPC 333 [(2R)-2-{(3R)-3-Amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide], a Human Tumor Necrosis Factor α-Converting Enzyme Inhibitor, on the Disposition of Methotrexate: A Transporter-Based Drug-Drug Interaction Case Study

Effect of DPC 333 [(2R)-2-{(3R)-3-Amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide], a Human Tumor Necrosis Factor α-Converting Enzyme Inhibitor, on the Disposition of Methotrexate: A Transporter-Based Drug-Drug Interaction Case Study

Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand on the Reduction of Joint Inflammation in Experimental Rheumatoid Arthritis

Pulmonary Function in Rheumatoid Arthritis Treated With Low-Dose Methotrexate: A Longitudinal Study

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