乙酸阴道热敏凝胶剂在家兔阴道内的药动学

Pharmacokinetics of acetic acid thermoreversible vaginal gel in rabbits vagina

目的研究乙酸阴道热敏凝胶剂经阴道给药后药物在家兔阴道内的药代动力学特征,探索适合阴道用药的新剂型。方法 3 ml含乙酸36.23 mg的乙酸阴道热敏凝胶剂推入家兔阴道内,给药后0.25,0.5,1,1.5,2,4,8,12,16,20和24 h,对家兔阴道进行灌洗并测定灌洗液中乙酸的含量、用微电极插入阴道测定阴道pH值、取阴道组织匀浆后测定组织中乙酸含量。采用非线性最小二乘法进行计算机拟合获得药动学参数。结果乙酸阴道热敏凝胶剂置入家兔阴道后,阴道pH值由给药前中性(pH 6.67)转变为酸性(pH 3.56),阴道pH 3.5～4.0可保持约6 h;pH 3.5～4.5可保持约12 h;pH 3.5～5.0可保持19 h;给药后24 h,pH值为5.32±0.24,乙酸含量为(0.38±0.15)g.L-1,为给药量的11%。阴道组织中乙酸浓度峰值为600μg.g-1,达峰时间为2 h,平均保留时间为7.73 h,药物动力学参数符合二室模型。结论乙酸阴道热敏凝胶剂符合阴道用药的要求。

OBJECTIVE To investigate the pharmacokinetics of acetic acid thermoreversible gel（Ace-Acid Gel） in rabbits vagina.METHODS Three microliter Ace-Acid Gel（containing 36.23 mg acetic acid） was given to the 66 rabbits through vagina.At 0.25,0.5,1,1.5,2,4,8,12,16,20 and 24 h after administration,acetic acid content in rabbit vaginal lavage fluid and in homogenated vaginal tissues were measured.Vaginal pH was detected with a microelectrode inserted into the vagina,and pharmacokinetic parameters were calculated using nonlinear least squares fitting model.RESULTS After Ace-Acid Gel administration,vaginal pH changed from neutral（pH 6.67） to acidic（pH 3.56）.The pH value was maintained at 3.5-4.0 for 6 h,at 3.5-4.5 for 12 h,and at 3.5-5.0 for 19 h.At 24 h,the pH value was 5.32±0.24 and the acetic acid content was（0.38±0.15）g·L-1（11% of administered dose）.The concentration-time curve fitted in with the two-compartment model.The peak concentration（cmax） of acetic acid in vaginal tissue was 600 μg·g-1,peak time（Tmax） was 2 h,and the mean residence time（MRT0-24） was 7.73 h.CONCLUSION The new formulation is suitable for vaginal delivery.