A PHARMACOKINETIC STUDY OF INTRAVENOUS CTLA4IG, A NOVEL IMMUNOSUPPRESSIVE AGENT, IN MICE

Three skin-intact mice in each group received a single 0.07-, 0.29-, o r 0.57-mg dose of CTLA4lg intravenously (iv). Three skin-grafted mice received a single 0.29-mg dose iv and another three skin-grafted mice received a 0.29-mg dose once daily for 7 days (the dose was administer ed via the tail vein). Serial blood samples (0.15 mL) were obtained by retro-orbital bleeds up to 240 h after all single doses and up to 360 h after the last multiple dose. Serum samples were analyzed for CTLA4 lg by a validated enzyme immunoassay method. The concentration data we re subjected to noncompartmental pharmacokinetic analysis. Both C-max and AUC(inf) values increased in a dose-proportional manner in skin-in tact mice. The CL(T) values were dose independent. The MRT, t(1/2), an d Vd(ss) values at the 0.07-mg dose level were significantly lower tha n those obtained for both the 0.29- and 0.57-mg dose levels; however, the respective values between the 0.29- and 0.57-mg dose levels were n ot significantly different. No significant differences were found in t he pharmacokinetic parameters between the skin-intact and skin-grafted mice.