Predicting Tacrolimus Concentrations in the Skin of Adult Kidney Transplant Recipients: A Feasibility Study

Area of Science:

• Pharmacology
• Dermatology
• Transplantation

Background:

• Solid organ transplant recipients face increased skin cancer risk due to immunosuppression, especially from calcineurin inhibitors like tacrolimus.
• Tacrolimus is a widely used calcineurin inhibitor in this population.
• Understanding tacrolimus levels in skin is crucial for developing skin cancer prevention and treatment strategies.

Purpose of the Study:

• To investigate tacrolimus pharmacokinetics in the skin of mice and kidney transplant recipients.
• To determine the correlation between tacrolimus blood and skin concentrations in humans.
• To explore the utility of blood tacrolimus levels for estimating skin concentrations.

Main Methods:

• Pharmacokinetic analysis of tacrolimus in mouse blood and skin after oral administration.
• Measurement of tacrolimus concentrations in skin biopsies and blood samples from kidney transplant recipients.
• Statistical correlation analysis between blood and skin tacrolimus levels.

Main Results:

• In mice, tacrolimus skin concentrations rose slowly and remained elevated for at least 6 hours post-dose, while blood levels peaked earlier.
• In kidney transplant recipients, skin tacrolimus concentrations ranged from 7.1 to 71.2 ng/g.
• A significant correlation (r=0.6) was observed between tacrolimus blood and skin concentrations in human subjects.
• Mean skin concentrations in mice and humans were comparable.

Conclusions:

• Tacrolimus exhibits prolonged retention in the skin compared to blood.
• Blood tacrolimus concentrations can serve as a surrogate marker for approximating skin tacrolimus levels in kidney transplant recipients.
• These findings support the potential use of blood monitoring to guide targeted anti-cancer therapies in the skin of transplant patients.