Effect of Renal Ischemia on Plasma Levels of FK 506 in Rats.

IT IS generally recognized that at steady-state conditions less than 10% of cyclosporine (CyA)1,2 or FK 5063 is excreted by the kidney and that renal function has little or no effect on the blood or plasma levels of either of these two drugs. Experimental studies, however, have shown that animals with severely impaired renal function have higher blood CyA trough levels than do controls.4,5 Therefore the presence of renal ischemia and/or nephrotoxicity may have an effect as yet unidentified on the regulation of the CyA or FK 506 blood level. To investigate this question, the effect of renal ischemia on single and multiple IV administration of FK 506 was studied in rats subjected to unilateral left nephrectomy and contralateral total renal ischemia.