A comprehensive review on immunosuppressant agent: Tacrolimus
Keywords:
Immunosuppressant, Pharmacogenomics, Tacrolimus, Calcineurin inhibitorAbstract
An immunosuppressive drug with great potency, tacrolimus (FK 506), has been shown to be effective in both in-vivo and in-vitro studies. As a calcineurin inhibitor, tacrolimus is also effective. The pharmacokinetics profile of tacrolimus is very variable across and within patients as a result of its low solubility. Numerous formulation strategies, including complexation with cyclodextrins, solid dispersions, oily solutions, liposomes, etc., have been researched to increase this agent's oral administration. Tacrolimus can be used to treat severe autoimmune disorders such atopic dermatitis and rheumatoid arthritis, and it has been given for patients who have undergone liver, intestine, lung, and heart transplants. Because it has a superior safety profile and a higher rate of long-term survival in patients than other immunosuppressants, tacrolimus is used the most commonly..
Downloads
References
Wang Y, Wang C, Fu S, Liu Q, Dou D, Lv H. Preparation of Tacrolimus loaded micelles based on Poly (e-caprolactone)-poly(ethylene-glycol)-poly (ecaprolactone).Int J.Pharm 2011;407:184-9
Ruzicka T, Bieber T, Schöpf E. A short-term trial of tacrolimus ointment for atopic dermatitis. N Engl J Med 1997; 337:816–821.
Toutous-Trellu L, Abraham S, Pechere M.Topical tacrolimus for effective treatment of eosinophilic folliculitis associated with human immunodeficiency virus infection. Arch Dermatol 2005; 141:1203–1208.
Baldo A, Prizio E, Mansueto G. A case of chronic actinic dermatitis treated with topical tacrolimus. J Dermatolog Treat 2005; 16:245–248.
Ginarte M, Toribio J. Vulvar lichen sclerosus successfully treated with topical tacrolimus. Eur J Obstet Gynecol Reprod Biol 2005; 123:123–124.
Brill TJ, Elshorst-Schmidt T, Valesky EM. Successful treatment of AcrodermatitiscontinuafHallopeau with sequential combination of calcipotriol and tacrolimus ointments. Dermatology 2005;211:351–355
Ali SM, Ahmad A, Sheikh S, Ahmad MU, Rane RC, Kale P. Polyoxyl 60 hydrogenated castor oil free nanosomal formulation of immunosuppressant
Tacrolimus: Pharmacokinetics, safety, and tolerability in rodents and humans.
IntImmunopharmacol 2010; 10:325‑30.
Chougule M, Padhi B, Misra A. Nanoliposomal dry powder inhaler of tacrolimus: Preparation, characterization, and pulmonary Pharmacokinetics. Int J Nanomed 2007; 2:675‑88.
McAlister VC, Keshava murthy M, Lee TD. Oral delivery of liposomal tacrolimus: Increased efficacy and reduced toxicity. Transplant Proc 1993; 31:1110.
Gershanik T, Benita S. Self-dispersing lipid formulations for improving oral absorption of lipophilic drugs. Eur J Pharm Bio-pharm 2000; 50:179‑88.
Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother 2004;58:173‑82
Pouton CW, Porter CJ. Formulation of lipid based delivery systems for oral administration: Materials, methods and strategies. Adv Drug Deliv Rev 2008; 60:625‑37.
Cornaire G, Woodley J, Hermann P, Cloare A, Arellano C, Houin G. Impact of excipients on the absorption of Glycoprotein substrates in vitro and in vivo. Int J Pharm 2004;278:119‑31
Wandel C, Kim RB, Stein CM. Inactive excipients such as Cremophor can affect in vivo drug disposition. ClinPharmacolTher 2003; 73:394‑6.
Charman WN. Lipid vehicle and formulation effects on intestinal lymphatic drug transport. In: Lymphatic transport of drugs. Boca Raton: CRC Press, 1992. 113‑79.
Venkataramanan R, Swaminathan A, Prasad T, Jain A,Zuckerman S, Warty V,
Clinical pharmacokinetics of tacrolimus. ClinPharmacokinet 1995; 29:404‑30.
Kershner RP, Fitzsimmons WE. Relationship of FK506 whole blood concentrations and efficacy and toxicity after liver and kidney transplantation. Transplantation 1996; 62:920‑6.
Duijnhoven E, Christiaans M, Undre N, Stevenson P,vanHooff J. The effect of breakfast on the oral bioavailability of tacrolimus in diabetic and nondiabetic patients before transplantation.TransplantProc 1998; 30:1268‑70.
Nakata Y, Yoshibayashi M, Yonemura T, Uemoto S, Inomata Y,Tanaka K.
Tacrolimus and myocardial hypertrophy.Transplantation 2000;69:1960‑62.
Morales JM, Andres A, Rengel M, and Rodicio JL. Influence of cyclosporin, tacrolimus and rapamycin on renal function and arterial hypertension after renal transplantation. Nephrol Dial
Transplant 2001; 16:121‑4.
Chenhsu RY, Loong CC, Chou MH, Lin MF, Yang WU. Renal allograft dysfunction associated with rifampin‑tacrolimus interaction. Ann Pharmacother 2000; 34:27‑31.
Hooks M. Tacrolimus, a new immunosuppressant: a review of the literature. Ann
Pharmacother 1994; 28:501–511.
Roy JN, Barama A, Poirier C, Vinet B, Roger M. Cyp3A4,Cyp3A5, and MDR‑1 genetic influences on tacrolimus pharmacokinetics in renal transplant recipients. Pharmacogenetic Genomic 2006; 16:659‑65.
Tamura S, Ohike A, Ibuki R, Amidon GL, Yamashita S. Tacrolimus a class‑II low solubility high permeability drug: The effect ogP‑glycoprotein efflux on regional permeability of tacrolimus in rats. J Pharm Sci 2002;91:719
Contreras Ruiz J, Kerdel FA. Tacrolimus (FK-506) In: Millikan LE, ed. Drug Therapy in Dermatology. 1st ed. New York, NY: Marcel Dekkar, Inc, 2004. 161-170.
Robles M, Santos-Beneit F, Martin JF. "Omic Approaches". Antibiotics 2018; 7:39.
Chen D, Zhang L, Pang B, Chen J, Xu Z, Abe I, Liu W,(2013)"FK506 maturation involves a cytochrome p450 protein-catalyzed four-electron C-9 oxidation in parallel with a C-31 Omethylation". J Bact 2013;195:1931
Mo S, Ban YH, Park JW, Yoo YJ, Yoon YJ (2009). "Enhanced FK506 production in Streptomyces clavuligerus CKD1119 by engineering the supply of methylmalonyl-CoA precursor". J Ind Micro Biotech 2009;36: 1473–82.
Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001;
13:123–133.
Patel P, Patel H, Panchal S, Mehta T. Formulation strategies for drug delivery of tacrolimus:
an overview, Int J Pharm Investig 2012;2:169.
Bertram G. Katzung, (2017), Basic and Clinical Pharmacology. 14th Edition, 2017. 985-986.
Laurence L. Brunton, John Lazo, Keith Parker. Goodman and Gilman, The pharmacological-
Basis of therapeutics,11th edition, 2011. 1405-1413.
Dheer D, Jyoti, Gupta P, Shankar R. Tacrolimus: An updated review on delivering strategies for multifarious diseases.Eur J Pharm Sci 2018; 114: 217–227.
Tavira B, Garcia E, Diaz corte C. Pharmacogenetics of tacrolimus after renal transplantation: Analysis of polymorphisms in genes encoding 16 drug metabolizing enzymes. Clin Chem Lab Med 2011; 49(5) 825-833.
Hesselink D, van Schaik R, van Agteren M. CYP3A5 genotype is not associated with a higher risk of acute rejection in Tacrolimus treated renal transplant recipients,pharmacogenetics and genomics. 2008;18: 339-348.
Mo S, Ban YH, Park JW, Yoo YJ, Yoon YJ "Enhanced FK506 production in
Streptomyces clavuligerus CKD1119 by engineering the supply of methylmalonylCoA precursor". Journal of Industrial Microbiology & Biotechnology. 2009;36(12): 1473–82.
Chen D, Zhang L, Pang B, Chen J, Xu Z, Abe I, Liu W. "FK506 maturation involves a cytochrome p450 protein-catalyzed four-electron C-9 oxidation in parallel with a C-31 O-methylation". Journal of Bacteriology, 2013; 195 (9): 1931–9.
"Advagraf EPAR". European Medicines Agency (EMA). Retrieved 29 April 2020.
Pritchard DI. "Sourcing a chemical succession for cyclosporin from parasites and human pathogens". Drug Discovery Today, 2015;10 (10): 688–91.
"Prograf: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 29
April 2020.
Kino T, Hatanaka H, Hashimoto M, Nishiyama M, Goto T, Okuhara M, Kohsaka M, Aoki H,
Imanaka H. "FK-506, a novel immunosuppressant isolated from a Streptomyces. I.
Fermentation, isolation, and physico-chemical and biological characteristics". The Journal of Antibiotics, 1987;40 (9): 1249–55.
Hatanaka H, Iwami M, Kino T, Goto T, Okuhara M. "FR-900520 and FR-900523, novel immunosuppressants isolated from a Streptomyces. I. Taxonomy of the producing strain". The Journal of Antibiotics,1988; 41 (11): 1586–91.
Benkali K, Prémaud A, Picard N, Rérolle JP, Toupance O, Hoizey G, Turcant A, Villemain F, Le Meur Y, Marquet P, Rousseau A."Tacrolimus population pharmacokinetic-
pharmacogenetic analysis and Bayesian estimation in renal transplant recipients". Clinical Pharmacokinetics,2009; 48 (12): 805–16.
Barbarino JM, Staatz CE, Venkataramanan R, Klein TE, Altman RB. "PharmGKB summary: cyclosporine and tacrolimus pathways". Pharmacogenetics and Genomics,2013;23(10): 563–85.
Staatz CE, Tett SE. "Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation". Clinical Pharmacokinetics,2004;43 (10): 623–53
Downloads
Published
How to Cite
Issue
Section
License

This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.