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

TL;DR

This study explores how tacrolimus, a drug used after kidney transplants, accumulates in the skin and how blood levels can predict skin concentrations, which may help prevent skin cancer in transplant patients.

Contribution

The study demonstrates that blood tacrolimus levels can approximate skin concentrations in kidney transplant recipients, offering a new approach for cancer prevention strategies.

Findings

Tacrolimus skin concentrations in mice rose slowly and remained high for at least 6 hours post-dose.

Human skin tacrolimus levels correlated with blood concentrations (r = 0.6).

Mouse and human skin tacrolimus concentrations were in a similar range.

Abstract

Solid organ transplant recipients are at an increased risk of developing skin cancers due to chronic immunosuppression, particularly with calcineurin inhibitors. Tacrolimus is the most prescribed calcineurin inhibitor in this patient cohort, and understanding tacrolimus concentrations in the skin will facilitate the development of anti-cancer preventive and therapeutic strategies. Here, we show that in mice, tacrolimus blood levels peaked rapidly ∼1 h post last oral dose while skin levels rose more slowly and remained high for at least 6 h. Subsequently, tacrolimus skin and blood concentrations were assessed in 15 kidney transplant recipients. The mean age was 61 years, the average time post-transplant was 7 years (range 0–21 years) and 87% were male. The average skin sampling time post tacrolimus dosing was 6 h 32 min. Skin tacrolimus concentrations ranged from 7.1 ng/g to 71.2 ng/g and correlated with blood concentrations (r = 0.6). Mouse and human mean skin concentrations were in a similar range. Our data suggests that tacrolimus measurements in the blood may be used to approximate tacrolimus concentrations in the skin of kidney transplant recipients, and further exploited for the delivery of anti-cancer therapies designed to antagonize the immunosuppressive effects of tacrolimus in the skin.

Figures