克林霉素磷酸酯阴道凝胶在健康志愿者的药代动力学

Pharmacokinetics of clindamycin phosphate vagina gel in Chinese healthy volunteers

目的研究克林霉素磷酸酯阴道凝胶(抗细菌性阴道病药)在健康女性受试者的药代动力学。方法健康女性志愿者10名,多剂量每次给予克林霉素磷酸酯阴道凝胶5g(相当于克林霉素100mg),每日1次,连续用药3日;而单剂是用量相同,1次给药。用HPLC-MS法测定血清中克林霉素浓度,用DAS药代动力学程序进行数据处理。结果克林霉素磷酸酯阴道凝胶单剂和多剂给药,符合一级消除药代动力学的二室模型,克林霉素主要药代动力学参数tmax分别为(4.88±0.94),(4.70±0.59)h;Cmax分别为(38.30±22.77),(44.87±26.71)ng·mL-1;t1/2分别为(15.30±2.62),(14.78±2.49)h;AUC0→∞分别为(783.45±351.19),(1015.68±456.95)ng·h·mL-1。结论克林霉素磷酸酯阴道凝胶单次和多次给药,Cmax降低,t1/2延长,提示该药以局部作用为主;亦可吸收入血,缓慢产生全身作用。

Objective To investigate the pharmacokinetics of clindamycin phosphate vagina gel in healthy Chinese female volunteers. Methods Ten healthy Chinese female volunteers were vaginally given with 5.0g of clindamycin phosphate vagina gel（ the equivalent to 100 mg of elindamycin） once for single dose treatment, and 5.0g,once a day for 3 days, for multiple dose treatment. The serum samples were determinded by HPLC - MS method. The pharmacokinetic parameters of clidamycin were calculated by DAS software. Results The main pharmaeokinetics parameters of clindamycin for single dose and multiple doses were as follow ： t1/2 were（ 15.30 ± 2.62） and（ 14.78 ±2.49） h, tmax were（4.88 ± 0.94） and （4.70 ± 0.59） h, Cmax were （ 38.30 ± 22.77 ） and （44.87 ± 26.71 ） ng·mL ^-1,AUC0-∞ were （783.45 ±351.19） and （1015.68 ±456.95） ng·h·mL-1, respectively. Conclusion The Cmax of elindamyein phosphate vagina gel after a single dose and multiple doses were obviously lower and t1/2 were longer than that of clindamycin phosphate oral preparations, which suggests that clindamycin phosphate vagina gel act topically and be absorbed slowly with systemic actions.