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QuickView for Tacrolimus (compound)


PubChem
Name: Tacrolimus
PubChem Compound ID: 11158639
Description: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.
Molecular formula: C44H69NO12
Molecular weight: 808.034 g/mol
DrugBank
Identification
Name: Tacrolimus
Name (isomeric): DB00864
Drug Type: small molecule
Description: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.
Synonyms:
FK5; K506; FK-506; Tacarolimus; tacrolimus hydrate
Brand: LCP-Tacro, Prograf, Fujimycin, Protopic
Category: Immunosuppressive Agents
CAS number: 104987-11-3
Pharmacology
Indication: For use after allogenic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It was first approved by the FDA in 1994 for use in liver transplantation, this has been extended to include kidney, heart, small bowel, pancreas, lung, trachea, skin, cornea, and limb transplants. It has also been used in a topical preparation in the treatment of severe atopic dermatitis.
Pharmacology:
Tacrolimus is a macrolide antibiotic. It acts by reducing peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This inhibits both T-lymphocyte signal transduction and IL-2 transcription. Although this activity is similar to cyclosporine studies have shown that the incidence of acu...
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Mechanism of Action:
The mechanism of action of tacrolimus in atopic dermatitis is not known. While the following have been observed, the clinical significance of these observations in atopic dermatitis is not known. It has been demonstrated that tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12. A complex of tacrolimus-F...
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Absorption: 20% bioavailability; less after eating food rich in fat
Protein binding: 75-99%
Biotransformation: Hepatic, extensive, primarily by CYP3A4. The major metabolite identified in incubations with human liver microsomes is 13-demethyl tacrolimus. In in vitro studies, a 31-demethyl metabolite has been reported to have the same activity as tacrolimus.
Route of elimination: In man, less than 1% of the dose administered is excreted unchanged in urine. Fecal elimination accounted for 92.6±30.7%, urinary elimination accounted for 2.3±1.1%.
Half Life: 11.3 hours (range from 3.5 to 40.6 hours)
Clearance: 0.029 +/- 0.009 L/hr/kg [healthy subjects IV administered] 0.172 +/- 0.088 L/hr/kg [Healthy subjects administered PO] 0.138 +/- 0.071 L/hr/kg [liver transplantation pediatric patients] 0.038 +/-0.014 L/hr/kg [patients with renal impairment 0.02 mg/kg/4 hr, IV] 0.042 +/- 0.02 L/hr/kg [Mild Hepatic Impairment 0.02 mg/kg/4 hr, IV] 0.034 +/- 0.019 L/hr/kg [Mild Hepatic Impairment 7.7 mg PO] 0.017 +/- 0.013 L/hr/kg [Severe hepatic impairement 0.02 mg/kg/4 hr, IV]
Toxicity: Side effects can be severe and include blurred vision, liver and kidney problems (it is nephrotoxic), seizures, tremors, hypertension, hypomagnesemia, diabetes mellitus, hyperkalemia, itching, insomnia, confusion. LD50=134-194 mg/kg (rat).
Affected organisms: Humans and other mammals
Interactions
Drug interaction:
PentamidineAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
FoscarnetAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
FelodipineFelodipine increases tacrolimus levels
SirolimusSirolimus may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Sirolimus therapy is initiated, discontinued or altered.
DofetilideAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
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