生物降解型左旋18-甲基炔诺酮微球在大鼠的药代动力学

用放射免疫法研究了左旋18-甲基炔诺酮(LNG)微球和LNG微晶在大鼠的药代动力学。大鼠单次imLNG微晶35mg·kg^-1后4.88h.血药峰值达67.66nmol·L^-1,MRT为10.16d,T_{<0.32nmol·L^-1}为41.50d;而单次imLNG微球20.4,41.1和83.3mg·kg^-1后,血药分别于6,4.67和4.33h达峰浓度15.19,33.61和38.55nmol·L^-1,MRT分别为69.23,65.12和63.25d,T_{<0.3nmol·L^-1}分别为167.81,169.73和167.23d。可见LNG微球在大鼠的MRT和T_{<0.32nmol·L^-1}分别约为LNG微晶的6.6和4.2倍,提示该微球具有明显的缓释长效作用,且初始血药峰值明显低于肌注LNG微晶。

PHARMACOKINETICS OF LEVONORGESTREL AFTER A SINGLE DOSE OF BIODEGRADABLE MICROSPHERES CONTAINING LEVONOFGESTREL IN RATS

Pharmacokinetics of levonorgestrel(LNG )in the form of injectable microspheres made of biodegradable co-polymer of polylactic acid and polyglycolic acid(9:1 PLGA)that contained 17.76%LNG,were tested in rats.Rats were given a single intramuscular injection(im )of LNG microspheres at doses of 20.4,41.1 and 83.3 mg·kg^-1.Six rats were treated with a single im of LNG microcrystals at dose of 35.0 mg·kg^-1.Plasma samples obtained before injection and at various time after injection were analyzed for LNG by RIA method. eak plasma LNG level of 67.66 nmol·L^-1 was obtained 4.88 h after im of LNG microcrystals, T_1/2=5.78d, MRT=10.16 d and T_{<0.32 nmol·L^-1}=41.50d. Plasma LNG levels among rats after im of three different doses of LNG microspheres showed simi- lar biphasic changes.C_maxl(the first phase)were 15.19,33.61 and 38.55 nmol·L^-1;T_P1 Were 6,4.67 and 4.33 h;Ctrough Were 1.21,4.36 and 9.06 nmol·L^-1;Ttrough Were 55,53.67 and 54. 83 d;Cmax2(the second phase)were 3.80,9.48 and 19.68 nmol·L^-1;T_p2 were 100.49,102.21 and 89.27 d;AUC were 440.27,1082.82 and 1931. 47 nmol·d·L^-1; MRT were 69.23,65.12 and 68.25d;T<0.32nmol·L^-1 Were 167.81,169.73 and 167.23 d after im of LNG microspheres in doses of 20.4, 41.1 and 83.3 mg(LNG)· kg^-1 , respectively·C_max1,C_trough,C_max2 and AUC showed significantly positive correlation with LNG dose, while T_p1,L_p2,T_trough,MRT and T_{<0.32nmol·L^-1} did not. The first phase peak plasma LNG levels of LNG microspheres were significantly lower than that of LNG microcrystals ,but MRT and T_{<0.32nmol·L^-1} were significantly longer than that of LNG microcrystals. Pharmacokinetics of LNG microspheres in rats indicate that 9 :1 PLGA microspheres containing LNG have remarkablely long-acting sustained release action.