Tacrolimus (TCR) has been introduced recently in the treatment and prevention of rejection in a variety of organs. Its hepatic metabolism occurs via cytochrome P450 3A4. An increase or decrease in the whole blood levels may occur if we use substances that inhibit or induce cytochrome P450 3A4 activity.
Tacrolimus-induced nephrotoxic changes, clinical presentation, and probably its mechanism are the same as those of cyclosporine nephrotoxicity.
The mechanisms underlying acute nephrotoxicity are not fully understood, but it is hypothesized that TCR induces an increase in renal vasoconstriction with afferent arteriolar constriction and a decrease in glomerular filtration rate. Thus, TCR stimulates endothelin synthesis and release from renal cells, alters prostaglandin metabolism, and produces lipid peroxidation of the cell membrane. The decrease in renal function and extrarenal toxicity correlate better with high blood levels of TCR than with high dosage.
CITA DEL ARTÍCULO Transplant Proc. 1999 Sep;31(6):2250-1