Elidel
Pimecrolimus. Novartis.

Schopf RE.

Johannes Gutenberg University, Department of Dermatology, Mainz, Germany. schopf hautklinik.klinik.uni-mainz.de

Pimecrolimus, an ascomycin macrolactam derivative, is an inhibitor of T-cell and mast-cell activation, developed and launched by Novartis for the potential treatment of psoriasis and allergic, irritant and atopic dermatitis. The topical formulation had been launched in the US by February 2002 for mild-to-moderate atopic dermatitis in patients aged two years and older. At that time, an oral formulation was in development for which launch was anticipated for 2006. In March 2002, pimecrolimus was approved in Denmark, becoming the first non-steroid prescription cream approved for patients from as young as 3 months of age through to adulthood. At this time, Novartis planned to seek approvals in other European countries during 2002 under the Mutual Recognition Procedure, and elsewhere around the globe. In December 2000, Merrill Lynch predicted sales of SFr 100 million in 2002, rising to SFr 330 million in 2004, and in February 2001, the analysts predicted sales of SFr 120 million in 2002, rising to SFr 574 million in 2005. Later in August 2001, Deutsche Bank estimated sales of SFr 150 million in 2002, rising to SFr 550 million in 2005. Following FDA approval in 2002, Morgan Stanley Dean Witter cautiously predicted sales of SFr 60 million rising to SFr 860 million by 2007.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12090545&dopt=Abstract pimecrolimus Elidel



Elidel
Pimecrolimus 1% cream (Elidel) for atopic dermatitis.

Bernard LA, Bergman JN, Eichenfield LF.

Pediatric and Adolescent Dermatology, Childrens' Hospital and Health Center, San Diego, CA, USA.

Pimecrolimus is an immunomodulating medication that inhibits production of inflammatory cytokines in the skin and this compound was specifically developed for the treatment of inflammatory skin diseases. Phase II and III clinical trials with the topical formulation of pimecrolimus (Elidel cream, Novartis) have shown that it is safe and effective for use in patients with atopic dermatitis (AD). The US FDA recently approved Elidel for use in patients >or=2 years of age and older with mild to moderate atopic dermatitis (AD).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12097994&dopt=Abstract pimecrolimus Elidel



Elidel
Platelet aggregation and intracellular calcium mobilisation responses are enhanced by cyclosporin A but not by pimecrolimus (SDZ ASM 981).

Fox SC, Judge HM, Allen BR, Heptinstall S.

Centre for Vascular Research, University of Nottingham, Cardiovascular Medicine, Queen's Medical Centre, Nottingham NG7 2UH, UK. sue.fox nottingham.ac.uk

It has been shown previously that cyclosporin A enhances platelet aggregation responses, particularly to adenosine diphosphate (ADP). In this investigation platelet responses to ADP in the presence of cyclosporin A and pimecrolimus (SDZ ASM 981), a new cell selective inhibitor of inflammatory cytokines, were determined. Measurements were performed in whole blood using a sensitive platelet counting method and in platelet-rich plasma (PRP) using a Biola laser aggregometer. The latter monitors both aggregate formation and aggregate size. In vitro studies were performed using recombinant hirudin as anticoagulant in order that physiological concentrations of divalent cation concentrations were maintained. Studies using both methods confirmed an enhanced aggregation response to ADP in the presence of cyclosporin A. In contrast, aggregation responses were not enhanced in the presence of pimecrolimus, either in PRP or in whole blood where a slight reduction of ADP-induced aggregation was seen at concentrations of pimecrolimus >10(-6) M. The effects of cyclosporin A and pimecrolimus on ADP-induced calcium mobilisation in platelets were determined using a flow cytometric method. A significant increase in intracellular calcium mobilisation was seen in the presence of cyclosporin A but not in the presence of pimecrolimus. Enhanced platelet aggregation responses to ADP observed in the presence of cyclosporin A may be a consequence of enhanced ADP-induced calcium mobilisation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12189022&dopt=Abstract pimecrolimus Elidel



Elidel
Pimecrolimus inhibits up-regulation of OX40 and synthesis of inflammatory cytokines upon secondary T cell activation by allogeneic dendritic cells.

Kalthoff FS, Chung J, Stuetz A.

Norvartis Research Institute, Department AID, Brunnerstrasse 59, A 1235 Vienna, austria. frank.kalthoff pharma.novartis.com

Pimecrolimus is a new non-steroidal inhibitor of T cell and mast cell activation. In the present study, we compared the potency of pimecrolimus and cyclosporin A (CyA) to inhibit cytokine synthesis of alloantigen-primed T cells and the expression of CD134 (OX40), an inducible co-receptor molecule thought to be critical for the survival and expansion of inflammation-mediating T cells. To mimic the physiological situation of recurrent antigenic stimulation, we have used dendritic cells (DC) as stimulators of purified CD4+ T cells in the primary and secondary allogeneic mixed lymphocyte culture (allo-MLC). Pimecrolimus inhibited surface expression of OX40 and prevented the up-regulation of CD25 and CD54 with a 10-fold higher potency compared to CyA. Similarly, 50% inhibition of allo-DC-mediated T cell proliferation by pimecrolimus was obtained at 0.55 nm, compared to about 12 nm for CyA. Furthermore, pimecrolimus blocked the increase of OX40 on primed T cells restimulated on day 10 in secondary allo-MLC. Allo-DC-primed T cells showed a restricted cytokine profile characterized by the production of TNF-alpha, IFN-gamma and IL-2 but low to undetectable levels of IL-4 and IL-10. The synthesis of TNF-alpha and IFN-gamma and the up-regulation of OX40 on T cells after secondary allogeneic stimulation were almost entirely blocked by 10 nm pimecrolimus. Taken together, pimecrolimus inhibits T cell proliferation and Th1 cytokine synthesis and also prevents the up-regulation of the OX40 co-receptor on primed T cells indicating its potential in the therapy of chronic inflammation and autoimmunity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12296857&dopt=Abstract pimecrolimus Elidel