环孢素与伊曲康唑在大鼠体内药动学的相互作用-药学(药理学)专业论文.docxVIP

8 8 Results: In group A 1，single oral dosing of CsA, Tmax=1(h), t1/2β=20.6±7.47 (h).As to group C (co-administrated immediately)and B2 (combined single dose of CsA with ICZ when ICZ approached the steady-state blood concentration),the AUC 0-∞of CsA were increased from （ 11.0±2.8）μg·h·mL-1 to（ 16.2±8.8）and（ 21.5±5.7）μg·h·mL-1 separately,increased by 47% and 95% (P 0.01). Compared with group A 1,the Cmax of CsA in group B2 increased from （1.76±0.29）μg·mL-1 up to（2.18±0.25）μg·mL-1 , increased by 23.9%, (P0.05）. In group B 1，single oral dosing of ICZ, Tmax=1(h), t1/2β=11.26±1.43(h).As to group C (co-administrated immediately)and A2(combined single dose of ICZ with CsA when CsA approached the steady-state concentration),the AUC 0-∞ of ICZ were increased from（4.2±2.9） μg·h·mL-1 to（ 5.5±4.5）μg·h·mL-1，（P0.05）and（ 6.7±3.8）μg·h·mL-1（P0.01）separately, increased by 31% and 61%. Compared with group B 1, the mean Cmax of group A2 increased from（0.70±0.31）μg·mL-1 to（0.94±0.43）μg·mL-1 , increased by 34% (P0.05). Conclusion: In rats, the co-administration of CsA and ICZ had significant mutual effects on many pharmacokinetic parameters. When one comes to the steady state concentration after multiple dose, the elimination half life of both drugs would significantly prolonged once co-administrated with the other one. Meanwhile the Cmax and bioavailability would be remarkable improved. The bioavailability would also be increased when co-administrated at the first dose. It was indicated that the clinical dosage should be reduced when they were used together. There should be close therapeutic drug monitoring and dosage adjustment is necessary according to the monitoring results,in order to assure medication safety and promote their transplantation success rate. Key words : Cyclosporine; Itraconazole; HPLC; Pharmacokinetic; CYP3A4 4 4 英文缩略词表 英文缩写 英文全称 中文名称 CsA Cyclosporine A 环孢素 ICZ Itraconazole 伊曲康唑 SPSS Statistical Package for Social Science 社会科学统计套装软件 P-gp Permeability glycoprotein