Kim Soo-Jin, Choi Hoo-Kyun, Suh Soon-Pal, Lee Yong-Bok
College of Pharmacy, Chonnam National University, 300 Yongbong-dong, Buk-gu, Kwangju 500-757, South Korea.
Eur J Pharm Sci. 2002 Jun;15(5):497-502. doi: 10.1016/s0928-0987(02)00048-9.
O/W-emulsion and microspheres containing cyclosporin A (CSA) were prepared to investigate the feasibility of developing new formulations. The pharmacokinetic and pharmacodynamic characteristics of these preparations were evaluated in rabbits and compared to two commercial products, Sandimmun Neoral for oral administration and CIPOL Inj. for intravenous administration. After oral or intravenous administration (10 mg/kg) to male rabbits, CSA concentration and lymphocyte population in whole blood were measured by TDxFLx and Coulter STKS, respectively. Total clearance (CL(t)) was increased after intravenous administration of CSA O/W-emulsion compared with intravenous administration of CIPOL Inj. In case of oral administration, AUC and bioavailability of CSA microspheres and O/W-emulsion were not significantly different (P>0.05) from those of Sandimmun Neoral, however, MRT and T(max) of CSA microspheres and O/W-emulsion were significantly increased (P<0.05). There were no significant differences in the area between the baseline and effect curves (ABEC) among these formulations (P>0.05), but the pharmacodynamic availability (F(PD)) of CSA O/W-emulsion was 5.51-fold higher than that of CIPOL Inj. and was significantly greater than that of Sandimmun Neoral (P<0.05). These results suggest that CSA microspheres and O/W-emulsion have sustained release characteristics and may be used as such formulations for oral or intravenous administration of CSA.
制备了含环孢素A（CSA）的水包油型乳剂和微球，以研究开发新制剂的可行性。在兔体内评估了这些制剂的药代动力学和药效学特性，并与两种市售产品进行比较，口服的新山地明（Sandimmun Neoral）和静脉注射的环孢素注射液（CIPOL Inj.）。对雄性兔口服或静脉注射（10mg/kg）后，分别通过TDxFLx和库尔特STKS（Coulter STKS）测量全血中CSA浓度和淋巴细胞数量。与静脉注射环孢素注射液相比，静脉注射CSA水包油型乳剂后总清除率（CL(t)）升高。口服时，CSA微球和水包油型乳剂的AUC和生物利用度与新山地明相比无显著差异（P>0.05），然而，CSA微球和水包油型乳剂的MRT和T(max)显著增加（P<0.05）。这些制剂之间基线和效应曲线之间的面积（ABEC）无显著差异（P>0.05），但CSA水包油型乳剂的药效学可用性（F(PD)）比环孢素注射液高5.51倍，且显著大于新山地明（P<0.05）。这些结果表明，CSA微球和水包油型乳剂具有缓释特性，可作为CSA口服或静脉给药的此类制剂。
