Pharmacokinetic and pharmacodynamic evaluation of cyclosporin A O/W-emulsion and microsphere formulations in rabbits.
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.
Kim
Soo-Jin
SJ
College of Pharmacy, Chonnam National University, 300 Yongbong-dong, Buk-gu, Kwangju 500-757, South Korea.
Choi
Hoo-Kyun
HK
Suh
Soon-Pal
SP
Lee
Yong-Bok
YB
D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004655:Emulsions; D008297:Male; D008863:Microspheres; D011817:Rabbits
D004655:Emulsions; D016572:Cyclosporine