Thalidomide in Lepra Reaction

Sheskin, J

doi:10.1111/j.1365-4362.1975.tb00145.x

Cited by 28 publications

(27 citation statements)

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“…Sedation alone may not explain the striking effects of thalidomide, since drugs with comparable hypnotic properties are not known to be effective in this regard. Presently, thalidomide is considered the first line drug for erythema nodosum leprae [20] and also useful in graft-versus-host disease [21,22], Some of these effects have been accounted for by its immunomodulating properties, especially towards its capacity to reduce tumor necrosis factor-a synthesis by monocytes [23]. Further studies are necessary to investigate whether the antipruritic effect of thalidomide is in some way related with its capacity to interfere with mediators of the inflammatory process.…”

Section: Discussionmentioning

confidence: 99%

Thalidomide for the Treatment of Uremic Pruritus: A Crossover Randomized Double-Blind Trial

Silva¹,

Viana²,

Lugon³

et al. 1994

Nephron

162

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Our observation that thalidomide administration to a dialysis patient with leprosy alleviated his pruritus led us to condut this short-term study to assess the efficacy of the drug in this regard. From 210 hemodialysis patients, 29 cases of refractory uremic pruritus were entered into the study. Patients were instructed to score their symptoms from 0 to 3, three times a day and assigned to receive thalidomide or placebo at bed time for 7 days. After a washout period of 7 days, drugs were crossed over. Response was defined as a reduction of at least 50% in the pruritus scoring. Eigtheen patients finished the study. In the first phase, 55% of patients responded showing a mean reduction in their pruritus scoring of 78% (p < 0.05 vs. placebo); no response to placebo was observed. A similar proportion of patients responded to thalidomide in the second phase with a mean reduction in their pruritus scoring of 81%. In conclusion, thalidomide can be a precious tool in the handling of uremic pruritus unresponsive to available therapy.

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Section: Discussionmentioning

confidence: 99%

Thalidomide for the Treatment of Uremic Pruritus: A Crossover Randomized Double-Blind Trial

Silva¹,

Viana²,

Lugon³

et al. 1994

Nephron

162

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“…After the drug was withdrawn from the market due to its teratogenicity, the surprising activity of thalidomide in reactive lepromatous leprosy stimulated further study (2). Thalidomide has recently been tried for many immunologic disorders, including rheumatoid arthritis (3), sarcoidosis (4), pyoderma gangraenosum (5), and chronic cutaneous lupus (6).…”

Section: Thalidomide Induces Apoptosis In Human Monocytes By Using a mentioning

confidence: 99%

Thalidomide Induces Apoptosis in Human Monocytes by Using a Cytochrome c-Dependent Pathway

Gockel

Lügering

Heidemann

et al. 2004

The Journal of Immunology

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Thalidomide has been shown to be an effective treatment in various immunologic diseases such as Crohn’s disease and rheumatoid arthritis. Its major effect is thought to be mediated by the inhibition of TNF-α, but the exact mechanism of action is still uncertain. Recent observations could demonstrate that the induction of monocyte apoptosis is a common feature of a variety of anti-inflammatory agents. Therefore, we investigated the role of thalidomide on monocyte apoptosis. Treatment with thalidomide resulted in apoptosis of human peripheral blood monocytes in a time- and dose-dependent manner as demonstrated by annexin V staining. Monocyte apoptosis required the activation of caspases, as combined stimulation by thalidomide together with the broad caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone markedly prevented monocyte cell death. Apoptosis was triggered by a CD95/CD95 ligand, TNF-RI, and TRAIL-R1 independent pathway with an inhibition of AKT-1 kinase and consecutive mitochondrial release of cytochrome c, followed by the proteolytic activation of initiator caspase-9 and effector caspase-3. Our data suggest that thalidomide-induced monocyte apoptosis is at least partially mediated by a mitochondrial signaling pathway and might contribute to the complex immunomodulatory properties of the drug.

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“…It does not cause depression of CNS neuronal function, like the barbiturates, but is thought to involve activation of sleep centres in the forebrain, thereby, giving it a safer CNS profile [7]. Until recently, thalidomide had never been approved in the US, but was used on a restricted basis to treat an acute inflammatory reaction of lepromatous leprosy (Hansen's Disease), erythema nodosum leprosum (ENL) [8]. The fever, weight loss and debility in ENL and other diseases may be a result of macrophage production of cytokines, specifically tumour necrosis factor alpha (TNF-h) [9,10].…”

Section: Introductionmentioning

confidence: 99%

Effect of a high-fat meal on thalidomide pharmacokinetics and the relative bioavailability of oral formulations in healthy men and women

Teo¹,

Scheffler²,

Kook³

et al. 2000

Biopharm. Drug Dispos.

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The effect of food on the oral pharmacokinetics of thalidomide and the relative bioavailability of two oral thalidomide formulations were determined in an open label, single dose, randomized, three-way crossover study. Five male and eight female healthy volunteers received a single oral dose of 200 mg Celgene thalidomide capsules under fasted and non-fasted conditions, and a single dose of 200 mg tablets of Serral thalidomide under fasted conditions. The high-fat meal resulted in a 0.5-1.5 h absorption lag time, an increased mean C(max), a decreased mean AUC and a delay in mean T(max). The Serral tablet formulation resulted in a lower mean C(max), and slower terminal decline in plasma thalidomide concentrations compared with both Celgene treatments. Mean C(max) concentrations were 1.99+/-0.41 microg/mL (range 1.28-2.76) within 4.00+/-1.13 h (2-5) for the Celgene formulation fasted, 2.17+/-0.51 microg/mL (1.43-3.01) within 6.08+/-2.33 h (3-12) for the Celgene formulation with food, and 1. 05+/-0.31 microg/mL (0.62-1.65) within 6.23+/-1.88 h (5-10) for the Serral formulation fasted. Mean terminal half-lives were 13.50+/-6. 77 h for the Serral product, compared with 5.80+/-1.72 h and 5. 09+/-1.03 h for Celgene fasted and fed, respectively. Celgene's formulation exhibited slightly greater bioavailability than Serral's formulation, with mean ratios of 122% and 110% for Ln-transformed AUC(0-t) and AUC(0-infinity), respectively. The mean C(max) for the Celgene formulation was approximately two times greater than Serral's. Food delayed the onset of absorption of by 0.5-1.5 h, but had little effect on the extent of absorption from the Celgene capsule. Under fasted conditions, the Celgene thalidomide resulted in a two-fold greater C(max) and 10% greater AUC(0-infinity) than the Serral formulation.

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Thalidomide in Lepra Reaction

Cited by 28 publications

References 1 publication

Thalidomide for the Treatment of Uremic Pruritus: A Crossover Randomized Double-Blind Trial

Thalidomide for the Treatment of Uremic Pruritus: A Crossover Randomized Double-Blind Trial

Thalidomide Induces Apoptosis in Human Monocytes by Using a Cytochrome c-Dependent Pathway

Effect of a high-fat meal on thalidomide pharmacokinetics and the relative bioavailability of oral formulations in healthy men and women

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