International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2014.487.493KisuIori KatoYojiro TsuchiyaHideaki KawamotoIkuo NakagawaTakahiro OgasawaraKazumasa HayakawaTomohisa YamayoshiYasuko IketaniOsamu MiharaMakoto BannoKouji SatoShin-ichi ShiinaTakashi AokiDaisuke 82014108Intramuscular or intravenous injection of Cyclosporine A (CyA) has been performed in some transplantation animal studies, including non-human primates. However, the pharmacokinetics after subcutaneous (s.c.) injection of CyA in cynomolgus monkey has not been reported. In this study CyA was administered subcutaneously in cynomolgus monkeys at three doses and investigated the pharmacokinetics. Six female cynomolgus monkeys were used in the study. CyA was administered once daily at a prescribed time for 7 days in the back of each monkey at doses of 2.5, 5 or 10 mg kg-1 in different administration periods. The blood trough level of CyA was measured on consecutive days. On days 0, 1 and 4, the level was measured 2, 4, 6, 8 and 12 h after CyA administration. The mean trough concentrations on day 4 in the 6 animals at doses of 2.5, 5 and 10 mg kg-1 were 162±56, 356±97 and 652±137 ng mL-1, respectively, showing a dose-dependent increase. The average Tmax range at each concentration on days 0 and 4 was 5-11 h and was 5-6 h on day 4 at steady state, with Cmax tending to be not high. The T1/2 showed general prolongations that were 14-19 h on day 4. Average pharmacokinetic data on day 4 showed dose-dependent and almost linear increases in AUC∞ which were 9822±3473, 24323±9520 and 43418±12591 ng.hr mL-1 at dose of 2.5, 5 and 10 mg kg-1, respectively. The pharmacokinetics of CyA after s.c. injection in cynomolgus monkeys showed a slow absorption phase, a Cmax that is not high and a prolonged elimination phase. The linearity of the AUC with dose and the high AUC and trough level in the early days after first administration suggest high bioavailability and sufficient efficacy after s.c. injection.]]>Aweeka, F.T., S.J. Tomlanovich, T. Prueksaritanont, S.K. Gupta and L.Z. Benet,1994346067De Waal, E.J., H.J. Schuurman, C. Hendriksen, B. Elvers, A. van Dijk and H. van Loveren,19921411011105Ducharme, M.P., L.H. Warbasse and D.J. Edwards,199557485491Hibi, T., M. Tanabe, K. Hoshino, Y. Fuchimoto and S. Kawachi et al.,201192100105Kisu, I., K. Banno, M. Mihara, N. Suganuma and D. Aoki,2013100280294Kisu, I., M. Mihara, K. Banno, H. Hara and Y. Masugi et al.,201440907918Ku, Y.M., D.I. Min and M. Flanigan,199838959965Kurlansky, P.A., A.M. Sadeghi, R.E. Michler, L.J. Coppey and L.P. Re et al., 19865312316Leonard, A.A., M. Jonker and E.L. Lagaaij,19966116481651Levy, G., P. Burra, A. Cavallari, C. Duvoux and J. Lake et al.,200273953959Winter, M.E.,2004pp: 45-48pp: 45-48Milliez, J.,2009106270270Novitzky, D., D.K. Cooper and W.N. Wicomb,198568737739Ogunnaike, H.O., T.D. Starkey, J.C. Baldwin, K.A. Porter, M.E. Billingham and S.W. Jamieson,1987431317Pennock, J.L., B.A. Reitz, C.P. Bieber, S. Aziz and P.E. Oyer et al.,198132467473Ptachcinski, R.J., R. Venkataramanan, G.J. Burckart, J.A. Gray, D.H. van Thiel, A. Sanghvi and J.T. Rosenthal,198727243248Sato, K., T. Iwane, S. Sekiguchi, A. Nakamura and Y. Akamatsu et al.,200941229232Schuurman, H.J., W. Slingerland, K. Mennninger, M. Ossevoort and J.C. Hengy,200114320328Shah, A.K., R.C. Brundage, A. Gratwohl and R.J. Sawchuk,199281491495