A Tale of Tacrolimus

Описание: Works Cited: The Evolution of Tacrolimus (FK506)
I. The Landmark "Day Zero" & Early Clinical Experience
FK 506 for liver, kidney, and pancreas transplantation
The Lancet | Starzl TE, Todo S, Fung J, et al.
Significance: The seminal paper detailing the first human use (March 1989) and the establishment of the "rescue phenomenon."
The Story of FK 506 Begins with Thomas E. Starzl
Editorial | Yilmaz
Significance: An editorial recounting the historical narrative of Starzl’s involvement and the "pilgrimage" to Japan.
Tacrolimus in liver transplantation
PubMed
Significance: Early review and data analysis establishing the drug as a standard in hepatic grafting.
II. The "Architecture of Evidence": Randomized Trials & Outcomes
The Pittsburgh randomized trial of tacrolimus compared to cyclosporine for hepatic transplantation
Fung JJ, et al. | Journal of Clinical Oncology
Significance: The pivotal study proving tacrolimus superiority (freedom from rejection) over cyclosporine.
Randomised trialomania? The multicentre liver transplant trials of tacrolimus
PubMed / PMC
Significance: A critical analysis of the early multicenter trials, addressing dosing controversies and the surgical "learning curve."
What Have We Learned About Primary Liver Transplantation Under Tacrolimus Immunosuppression? Long-Term Follow-up of the First 1000 Patients
Annals of Surgery | Jain A, Fung JJ, Starzl TE
Significance: A landmark long-term follow-up study defining the "chronic" era of tacrolimus use.
Primary Adult Liver Transplantation Under Tacrolimus: More Than 90 Months Actual Follow-Up Survival and Adverse Events
Jain A, et al.
Significance: Longitudinal data establishing the durability of tacrolimus-based grafts.
Tacrolimus and transplantation: A decade in review
Scott LJ, et al.
Significance: A comprehensive retrospective looking at the first ten years of the drug's global impact.
III. Expanding the Boundaries: Intestine & Multivisceral
Clinical Intestinal Transplantation: A Decade of Experience at a Single Center
Abu-Elmagd K, et al.
Significance: Documents the Pittsburgh experience in making the "forbidden" organ (intestine) transplantable.
Clinical intestinal transplantation in 1998: Pittsburgh experience
Abu-Elmagd K
Significance: Specific outcomes data on "grape cluster" and isolated intestinal grafts.
Clinical Intestinal Transplantation: New Perspectives and Immunologic Considerations
PMC
Significance: Discusses the immunological basis for intestinal grafting and GVHD prevention.
The Many Faces of Multivisceral Transplantation
Starzl TE, et al.
Significance: Foundational paper on the feasibility of multivisceral grafts.
IV. Discovery, Mechanism & Pharmacology
Draft Genome of Streptomyces tsukubaensis NRRL 18488, the Producer of Tacrolimus (FK506)
ResearchGate
Significance: The genetic characterization of the soil bacterium found near Mount Tsukuba.
Streptomyces tsukubensis VKM Aс-2618D—an Effective Producer of Tacrolimus
PMC
Significance: Research on the production and biology of the producing strain.
Renal Deletion of 12 kDa FK506-Binding Protein Attenuates Tacrolimus-Induced Hypertension
PMC
Significance: Mechanistic study exploring the side-effect profile (nephrotoxicity/hypertension) via the FKBP-12 pathway.
Production of tacrolimus using coconut oil as an alternative to glucose
Redalyc
Significance: Industrial and biosynthetic optimization of the drug.
V. Regulatory & Historical Context
Tacrolimus (FK506) and the Pharmaceutical/Academic/Regulatory Triangle
PMC
Significance: Explains Starzl’s strategy of collaboration between Fujisawa, Pittsburgh, and the FDA.
FDA Expands Indication for PROGRAF for Prevention of Organ Rejection in Lung Transplant Recipients
Astellas Press Release
Significance: The 2021 approval marking the evolution of the drug into lung transplantation.
Astellas Receives FDA Approval for Use of Prograf (Tacrolimus) in Conjunction With Mycophenolate Mofetil
Fierce Biotech
Significance: Marks the shift to the modern "standard of care" combination therapy.
Thomas E. Starzl: Transplantation pioneer
PMC
Significance: Biographical context on the surgeon who championed the drug against initial skepticism.