30例健康志愿者口服双环醇片剂的药代动力学研究

Pharmacokinetic study of bicyclol in thirty health volunteers

目的 研究健康志愿者口服双环醇片剂的药代动力学。方法 30名健康志愿者 ,随机分成 2 5、 5 0、10 0mg3个剂量组 ,分别给予单一剂量、多次剂量、餐前、餐后给药 ,用HPLC测定血药浓度 ,用3p97软件进行药代动力学分析。结果 药代动力学符合一房室模型及一级动力学消除规律 ,3个剂量单次给药代动力学参数分别为t( 1/2 )ka(0 .84±0 .6 8)、(0 .33± 0 .0 9)、(1.19± 10 .9)h。t( 1/2 )ke为(6 .2 6± 6 .2 4 )、(6 .17± 2 .0 1)、(4.6 6± 1.2 1)h。Vd/F 为 (45 5 .0 2± 135 .35 )、(6 2 2 .94± 32 5 .37)、(6 88.83± 30 8.14 )L。CL/F为 (93.4 5± 6 7.6 6 )、(83.31± 71.97)、(10 4 .30± 4 5 .76 )L·h- 1。cmax和AUC与剂量成正比。单次和多次口服双环醇片剂的药代动力学参数比较无显著差异。表明在一定剂量范围内 ,体内无蓄积现象。餐前、餐后的cmax分别为 (15 1.2 6± 39.0 0 )和 (2 2 2 .6 4± 4 3.2 2 ) μg·L- 1(P<0 .0 1) ,但AUC0～∞ 无明显差异 ,这可能与双环醇片剂的脂溶性有关。结论 双环醇片剂的药代动力学符合线性动力学特征 。

Aim To observe the pharmacokinetic profiles of oral administration of bicyclol in 30 healthy volunteers. Methods Thirty healthy volunteers were randomized into 25 mg, 50 mg and 100 mg groups. They were given bicyclol in a single dosage or multiple dosages before and after meal respectively. The plasma concentration of bicyclol was assayed by the high performance liquid chromatograply (HPLC). The pharmacokinetic parameters were analysed by 3p97 softwere. Results The feature of pharmacokinetics conformed to one compartment model and a first order elimination. For the three dose groups of 25, 50 and 100 mg , the values of t (1/2)ka were ( 0.84 ± 0.68) ? ( 0.33 ± 0.09) and ( 1.19 ± 10.9 ) h , respectively; the values of t (1/2)ke were ( 6.26 ± 6.24) , ( 6.17 ± 2.01) and ( 4.66 ± 1.21) h , respectively; V d/F ( 455.02 ± 135.35) , ( 622.94 ± 325.37) and ( 688.83 ± 308.14) L ; CL/F ( 93.45 ± 67.66) ? ( 83.31 ± 71.97) ? ( 104.30 ± 45.76) h . Between single dose and multiple dosages, the pharmacokinetic parameters had no significant difference, showing there was no accumulation in the body. Before and after meal, the values of c max were ( 151.26 ± 39.00 ) and ( 222.64 ± 43.22 ) μg·L -1 , respectively (P< 0.01 ), but the AUC 0～∞ had no significant difference,which was probabily related to the lipotroph of bicyclol. Conclusion Bicyclol has a linear pharmacokinetic feature. The absorption of bicyclol is influenced by food.