Tacrolimus

Tacrolimus
Clinical data


Trade names	Prograf, Advagraf, Protopic
Pregnancy category	AU: C US: C (Risk not ruled out)
Routes of administration	Topical, oral, iv
ATC code	D11AH01 (WHO) L04AD02 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	24% (5–67%), less after eating food rich in fat
Protein binding	≥98.8%
Metabolism	Hepatic CYP3A4, CYP3A5
Biological half-life	11.3 h for transplant patients (range 3.5–40.6 h)
Excretion	Mostly faecal
Identifiers
IUPAC name 3S-[3R^[E(1S^,3S^,4S^)] ,4S^,5R^,8S^,9E,12R^,14R^,15S^,16R^,18S^,19S^,26aR^ -5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a -hexadecahydro-5, 19-dihydroxy -3-[2-(4-hydroxy-3-methoxycyclohexyl) -1-methylethenyl]-14,16-dimethoxy -4,10,12,18-tetramethyl-8-(2-propenyl) -15,19-epoxy-3H-pyrido[2,1-c] [1,4] oxaazacyclotricosine-1,7,20,21(4H,23H) -tetrone, monohydrate
CAS Number	104987-11-3^Y
PubChem CID	6473866
DrugBank	DB00864^Y
ChemSpider	4976056^Y
UNII	Y5L2157C4J
KEGG	DG00439^N
ChEMBL	CHEMBL269732^N
ECHA InfoCard	100.155.367
Chemical and physical data
Formula	C₄₄H₆₉NO₁₂
Molar mass	804.018 g/mol
3D model (Jmol)	Interactive image
SMILES O=C3C(=O)N1CCCC[C@H]1C(=O)O[C@H](C(=C/[C@@H]2CC[C@@H](O)[C@H](OC)C2)/C)[C@H](C)[C@@H](O)CC(=O)[C@@H](/C=C(/C[C@@H](C[C@H](OC)[C@H]4O[C@]3(O)[C@H](C)C[C@@H]4OC)C)C)C\C=C
InChI InChI=1S/C44H69NO12/c1-10-13-31-19-25(2)18-26(3)20-37(54-8)40-38(55-9)22-28(5)44(52,57-40)41(49)42(50)45-17-12-11-14-32(45)43(51)56-39(29(6)34(47)24-35(31)48)27(4)21-30-15-16-33(46)36(23-30)53-7/h10,19,21,26,28-34,36-40,46-47,52H,1,11-18,20,22-24H2,2-9H3/b25-19-,27-21+/t26-,28+,29+,30-,31+,32-,33+,34-,36+,37-,38-,39+,40+,44+/m0/s1^Y Key:QJJXYPPXXYFBGM-LJIGMGMYSA-N^Y
^NY (what is this?)

Tacrolimus (also FK-506 or fujimycin, trade names Prograf, Advagraf, Protopic) is an immunosuppressive drug used mainly after allogeneic organ transplant to lower the risk of organ rejection. It achieves this by inhibiting the production of interleukin-2, a molecule that promotes the development and proliferation of T cells, which are vital to the body's learned (or adaptive) immune response. Tacrolimus is also used in the treatment of other T cell-mediated diseases such as eczema (for which it is applied to the skin in a medicated ointment), severe refractory uveitis after bone marrow transplants, exacerbations of minimal change disease, Kimura's disease, and the skin condition vitiligo.

Chemically it is a 23-membered macrolide lactone that was first discovered in 1987 from the fermentation broth of a Japanese soil sample that contained the bacterium Streptomyces tsukubaensis.

It has similar immunosuppressive properties to ciclosporin, but is much more potent. Immunosuppression with tacrolimus was associated with a significantly lower rate of acute rejection compared with ciclosporin-based immunosuppression (30.7% vs 46.4%) in one study. Clinical outcome is better with tacrolimus than with ciclosporin during the first year of liver transplantation. Long-term outcome has not been improved to the same extent. Tacrolimus is normally prescribed as part of a post-transplant cocktail including steroids, mycophenolate, and IL-2 receptor inhibitors such as basiliximab. Dosages are titrated to target blood levels.

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