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Inhibidores de Calcineurina

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by Carlos Peralta on 30 November 2012

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Transcript of Inhibidores de Calcineurina

Calcineurin Inhibitors.
Topic use Macrolidos Inmunomoduladores ISA247 (Isotechnika, Edmonton, AB, Canada) 1) Binds more tightly to calcineurin
than does ciclosporin, leading to a more complete
inhibition of calcineurin
2) the metabolism has been shifted away from aminoacid-1, which
is the major site of metabolism for ciclosporin Resumen Cyclosporin A.
Oral: Neoral. Novartis, Swiss

Topic: Ciclosporin. ISDIN, Spain

Voclosporin
Oral: ISA247. Isotechnika, Canada

Tacrolimus.
Oral: FK506. Prograft. Astellas, Japan

Topic: Protopic. Astellas, Japan

Pimecrolimus.
Topic: ASM 981 Elidel. Meda, Sweeden

Oral: ASM. Novartis, Swiss This shift leads to a faster elimination of metabolites and a lower drug and metabolite load after the administration of ISA247 than with ciclosporin. In animal models, ISA247 was more potent and had a more favourable side-eff ect profile than ciclosporin, particularly with regards to renal toxicity Abel MD, Aspeslet LJ, Freitag DG, et al. ISATX247: a novel calcineurin inhibitor. J Heart Lung Transplant 2001; 20: 161.
Aspeslet L, Freitag D, Trepanier D, et al. ISA(TX)247: a novel calcineurin inhibitor. Transplant Proc 2001; 33: 1048–51. Voclosporin ISA247 (Isotechnika, Edmonton, AB, Canada) Finantial Disclosure Clyclosporin A Carlos Peralta
Médico Dermatólogo

cperalta@intramed.net Hospital de Clínicas "José de San Martín" Pimecrolimus vs Tacrolimus Increase of pimecrolimus and tacrolimus concentrations
in the receptor fluid following permeation through human skin in vitro. Surface lipophilicity distribution of tacrolimus and pimecrolimus. Brown, green, and blue areas indicate lipophilic, intermediate,
and hydrophilic regions, respectively. The location of markedly different lipophilicity of the two molecules are indicated by the arrows. Penetration of pimecrolimus and tacrolimus into rat, pig, and
human skin in vitro after application as 1% solutions in propylene
glycol:oleyl alcohol (9:1). (A) Skin concentrations (epidermis and
dermis, after removal of stratum corneum). (B) Permeation rates. Tacrolimus. FK506 Tacrolimus es derivado de 'Tsukuba macrolide immunosuppressant' Es un macrólido con un anillo de lactona de 23 miembros, descubierto en 1984 del caldo de fermentación de una muestra de suelo japonés que contenía la bacteria Streptomyces tsukubaensis pimecrolimus has been shown to
affect keratinocyte function directly,A Phase I, Single-Center, Randomized, Vehicle-Controlled Study, Double-Blind for the Study Preparations and Observer-Blind for the Comparators to Determine the Antipsoriatic Efficacy and Tolerability of Topical Formulations With Ciclosporin in a Psoriasis Plaque Test Drug: Ciclosporin 0.5% (Formulation 01B)
Drug: Ciclosporin 1.5% (Formulation 02B)
Drug: 0.1% betamethasone
Drug: 0.005% calcipotriol ISDIN en el Bioskin Institut de Hamburgo en pacientes con psoriasis ha mostrado prometedores resultados de eficacia y seguridad de la innovadora formulación tópica de ciclosporina basada en la tecnología Dermosome Technology™ de la biotecnológica Advancell. La ciclosporina tópica es el primer proyecto en fase clínica que nace del acuerdo de colaboración entre ISDIN y la biotecnológica Advancell para el desarrollo de medicinas innovadoras en el tratamiento de la piel. La nueva tecnología empleada - DT Pimecrolimus Pimecrolimus 1%. (Elidel cream) is currently not indicated for use in Psoriasis Occlusion:
vs Clobetasol
vs Placebo.
Oral: 20 o 30 mg bid

Inverse Psoriasis
Facial Psoriasis Suggest that topical pimecrolimus does not act primarily by
inhibiting the calcineurin NFAT axis in lymphocytes but may instead act by other
mechanisms, possibly by decreasing NFAT2 activity in follicular keratinocytes. Pimecrolimus has been shown to
affect keratinocyte function directly, Mrowietz,U. et al. The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion. Br. J. Dermatol. 139, 992-996 (1998).
Mrowietz,U. et al. An experimental ointment formulation of pimecrolimus is effective in psoriasis without occlusion. Acta Derm. Venereol. 83, 351-353 (2003).
Rappersberger,K. et al. Pimecrolimus identifies a common genomic anti-inflammatory profile, is clinically highly effective in psoriasis and is well tolerated. J Invest Dermatol. 119, 876-887 (2002).
Gottlieb,A.B. et al. Oral pimecrolimus in the treatment of moderate to severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding trial. Br. J Dermatol. 152, 1219-1227 (2005).
Lin,A.N. Innovative use of topical calcineurin inhibitors. Dermatol Clin. 28, 535-545 (2010).
Gribetz,C. et al. Pimecrolimus cream 1% in the treatment of intertriginous psoriasis: a double-blind, randomized study. J. Am. Acad. Dermatol. 51, 731-738 (2004).
Jacobi,A., Braeutigam,M., Mahler,V., Schultz,E., & Hertl,M. Pimecrolimus 1% cream in the treatment of facial psoriasis: a 16-week open-label study. Dermatology. 216, 133-136 (2008). Inhibidores de la Calcineurina
-Ciclosporina
-Tacrolimus
-Pimecrolimus
-Ascrolimus
- Voclosporin No Inhibidores de la Calcineurina
-Sirolimus (Rapamicina)
-Everolimus (SDZ RAP) Calcineurina

Proteína Fosfatasa fijadora de Calcio
Activa al unirse a la calmodulia

-Aprendizaje y memoria
-Mantenimiento de la función renal
-Respuesta inmune Volumen 28 (2005)
Revisiones terapéuticas
Inhibidores de la calcineurina en dermatología: pasado, presente y futuro
por: Peralta C; Allevato MA
Hospital de Clínicas, Universidad de Buenos Aires
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