Pimecrolimus

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Pimecrolimus
Systematic (IUPAC) name
(3S,4R,5S,8R,9E,12S,14S,15R,16S,18R,19R,26aS) -3-{(E)-2-[(1R,3R,4S)-4-Chloro-3 -methoxycyclohexyl]-1-methylvinyl} -8-ethyl-5,6,8,11,12,13,14,15,16,17,18 ,19,24,25,26,26a-hexadecahydro -5,19-dihydroxy-14,16-dimethoxy -4,10,12,18-tetramethyl-15,19-epoxy -3H-pyrido[2,1-c][1,4]oxaazacyclotricosine -1,7,20,21(4H,23H)-tetrone
Identifiers
CAS number	137071-32-0
ATC code	D11AX15
PubChem	6447131
DrugBank	APRD01182
Chemical data
Formula	C43H68ClNO11
Mol. mass	810.453 g/mol
Pharmacokinetic data
Bioavailability	low systemic absorption
Protein binding	74%–87%
Metabolism	Hepatic CYP3A
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	topical

Pimecrolimus is an immunomodulating agent used in the treatment of atopic dermatitis (eczema). It is currently available as a topical cream, once marketed by Novartis, (however Galderma will be promoting the molecule in Canada in early 2007) under the trade name Elidel.

Contents 1 Pharmacology 2 Side effects 3 Footnotes 4 External links

[edit] Pharmacology

Pimecrolimus is an ascomycin macrolactam derivative. It has been shown in vitro that pimecrolimus binds to macrophilin-12 and inhibits calcineurin. Thus pimecrolimus inhibits T-cell activation by inhibiting the synthesis and release of cytokines from T-cells. Pimecrolimus also prevents the release of inflammatory cytokines and mediators from mast cells.

[edit] Side effects

See also: Immunomodulators in the treatment of eczema

In January 2006, the United States Food and Drug Administration (FDA) announced that Elidel packaging would be required to carry a black box warning regarding the potential increased risk of lymph node or skin malignancy, as for the similar drug tacrolimus. Whereas current practice by UK dermatologists is not to consider this a significant real concern and they are increasingly recommending the use of such new drugs.^[1]

Dermatologists' and Allergists' professional societies, the American Academy of Dermatology[1], and the American Academy of Allergy, Asthma, and Immunology, have protested the inclusion of the black box warning. The AAAAI states "None of the information provided for the cases of lymphoma associated with the use of topical pimecrolimus or tacrolimus in AD indicate or suggest a causal relationship."[2]. In light of the known side effects of steroids which are used first line for many dermatological conditions, many doctors prefer to use this drug instead. In practice, other doctors use the drug as a second-line remedy only after conventional methods of treatment have failed.

[edit] Footnotes

1. ^ N H Cox and Catherine H Smith (December 2002). Advice to dermatologists re topical tacrolimus (DOC). Therapy Guidelines Committee. British Association of Dermatologists.

[edit] External links

• Elidel official homepage
• FDA News
• NPS RADAR
• Offers more information on possible cancer risks of Elidel (Pimecrolimus)
• Article about American Academy of Dermatology speaking out against black box warning
• Report of the Calcineurin Task Force of the ACAAI and AAAAI

v • d • e Other dermatological preparations (D11) Medicated shampoos Cetrimide - Cadmium compounds - Selenium compounds - Povidone-iodine - Sulfur compounds - Xenysalate Other dermatologicals seborrhoeic dermatitis/dandruff (Lithium succinate, Pyrithione zinc) skin whitening/depigmenting (Hydroquinone, Mequinol, Monobenzone) anti-inflammatory/Immunomodulators (Oxaceprol, Gamolenic acid), Pimecrolimus, Tacrolimus) baldness treatments (Finasteride, Minoxidil) hair growth inhibiting agent (Eflornithine) other (Calcium gluconate, Magnesium sulfate, Tiratricol)