In Vivo Activity of Leflunomide

Chong, Anita S.; Huang, Wentao; Liu, Wei; Luo, J.; Shen, Jikun; Xu, Wei; Ma, Lianli; Blinder, Leonard; Xiao, Fei; Xu, Xiulong; Clardy, Christopher; Foster, Patricia L.; Williams, James A.

doi:10.1097/00007890-199907150-00020

Cited by 90 publications

(21 citation statements)

References 23 publications

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“…The authors speculate that the vasculoprotective effects are independent of its immunosuppressive effect and are linked to inhibition of tyrosine kinase and possibly platelet-derived growth factor. These findings support earlier work indicating that FK778 inhibits neointima formation by way of a mechanism that may be related to tyrosine kinase inhibitory activity in vascular smooth muscle cells (32).…”

Section: Modified-release Tacrolimus (Mr-4)supporting

confidence: 91%

New Drugs to Improve Transplant Outcomes

First¹,

Fitzsimmons²

2004

Transplantation

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Fujisawa is committed to improving the outcomes of transplant patients worldwide. Research and development programs are underway for a new modified release dosage form of tacrolimus (MR-4), a new analog of leflunomide (FK 778), and several novel compounds (PG 490-88, AGI 1096) in collaboration with other companies. These programs are targeted to address many of the unmet medical needs in transplantation including (1) improving compliance, (2) reducing chronic rejection, and (3) improving long-term safety by reducing infectious and cardiovascular risk.

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Section: Modified-release Tacrolimus (Mr-4)supporting

confidence: 91%

New Drugs to Improve Transplant Outcomes

First¹,

Fitzsimmons²

2004

Transplantation

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“…The leflunomide and sepsis + leflunomide groups were administered leflunomide 10 mg/kg (Arava, Aventis Pharmaceuticals) intragastrically in two doses with an 8 h interval prior to the experiment, because the peak concentration is 6-8 h [11]. Control, sham and sepsis groups were administered equal volume of saline in the same manner.…”

Section: Animalsmentioning

confidence: 99%

Does leflunomide attenuate the sepsis-induced acute lung injury?

et al. 2008

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The organ that is affected first and most severely in intraabdominal sepsis is the lung. Oxygen radicals and active neutrophils in the lung are important sources for severe pulmonary inflammation leading to acute lung injury (ALI)/acute respiratory distress syndrome. The aim of this study was to investigate the effects of leflunomide, an immunomodulatory agent, on oxidant/antioxidant status with nitric oxide (NO) level and myeloperoxidase (MPO) activity in rats with sepsis-induced ALI. Fifty male Wistar albino rats were divided into five groups: control, sham, sepsis, leflunomide (10 mg/kg, intragastrically for two doses with an 8 h interval prior to the experiment) and sepsis + leflunomide. After the animals were anesthetized with ketamine and xylazine, the abdominal cavity was opened and ligated just below the ileocaecal valve with 3-0 silk. The antimesentric surface of the cecum was perforated and the cecum was gently compressed until fecal matter was extruded to induce sepsis. None of the rats received antibiotics during the experimental procedures. The experiment was ended 24 h after cecal ligation puncture (CLP) with the cervical dislocation under anesthesia. The lung tissues were removed for analysis of biochemical parameters and light microscopic investigation. The lung superoxide dismutase (SOD), catalase and glutathione peroxidase activities were decreased in the sepsis group as compared to the group control, sham, leflunomide and sepsis + leflunomide (P < 0.05), and SOD activity were significantly higher in group sepsis + leflunomide than sham, control, leflunomide and sepsis group (P < 0.05). The lung MPO, malondialdehyde (MDA), protein carbonyl and NO levels were higher in the sepsis group when compared to group control, sham, leflunomide and sepsis + leflunomide (P < 0.05), and MPO, MDA and NO levels were higher in the sepsis + leflunomide group than in the sham, control and leflunomide group (P < 0.05). The light microscopic evaluation showed that pulmonary architecture was preserved, and infiltration of neutrophil and edema decreased in sepsis + leflunomide group. The grade of alveolar damage was significantly decreased in sepsis + leflunomide group in comparison with sepsis group (P < 0.05). Our findings suggested that leflunomide attenuated the lung injury after CLP-induced sepsis by inhibition of neutrophils accumulation and increasing endogenous antioxidant capacity.

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“…Leflunomide was given at a dose of 5 mg/kg in the rejection study. In the CMV study leflunomide was dosed at 30 mg/kg per day, a dose previously shown to produce the blood level of A77 1726 needed for viral inhibition in vitro and to be well tolerated for at least 30 days (16).…”

Section: General Carementioning

confidence: 99%

“…To obtain adequate uridine blood levels, large doses are required but with repeated oral dosing many of the rats develop uracil calculi in the kidneys. To avoid this, the uridine was given by intraperitoneal (IP) injection for which its pharmacokinetic behavior has been defined (16). Uridine was given once daily IP at 250 mg/kg in a total volume of 200 uL or less.…”

Section: General Carementioning

confidence: 99%