Human Pharmacokinetics of Fty 720

791 A myriocin derivative, FTY 720 is the first member of a unique immunosuppressant class to be developed for organ transplantation. The following is a preliminary report from the first in human trial on the pharmacokinetics of FTY 720. Methods. This study utilized a randomized, double-blind, placebo-controlled, time-lagged, two center design that explored doses from 0.25 to 3.5 mg. The 22 subjects in this report were stable renal transplant patients, ≥12 months post transplant, age 18-65, on Neoral® based immunosuppression, with serum creatinine ≤3.0. Whole blood FTY 720 concentration was measured by LC/MS/MS (LOQ 0.065 ng/mL) at multiple time points during a 96 hour period post dose. Results. The pharmacokinetic properties of FTY 720 are shown in the following table [Tmax (median, hr.). Cmax (mean, ng/mL), AUC0-∞ (mean, ngxhr/mL) and T1/2 (mean, hr.)(C.V. in parentheses)].TableFTY 720 was absorbed slowly with a lag time of approximately 0.5 to 2 hours. The apparent volume of distribution (Vd/F) and clearance (CLt/F) were consistent across all dose cohorts and ranged from 1116-1737 L and 140-200 mL/min, respectively. Conclusions. Cmax and AUC0-∞ were proportional to dose indicating that, over the dose range of 0.25 to 3.5 mg, the pharmacokinetic properties of FTY 720 were linear. The Vd/F is well in excess of blood volume, consistent with widespread tissue distribution. The long T1/2 suggests significant potential for an extended pharmacologic effect. The intersubject variability of FTY 720 pharmacokinetics is low, indicating a consistent absorption and disposition of this compound across subjects.