川芎嗪对大鼠灌服环孢素A药代动力学的影响

目的研究中药成分川芎嗪(TMP)对大鼠灌服环孢素A(CsA)药代动力学的影响。方法40只雄性SD大鼠按体重进行随机区组设计，分为4组。试验d 1，每只大鼠灌服CsA(10 mg·kg^-1)后，于0，1，2，3,4，6，8，12，24，36和48 h从尾静脉处采血0.2～0.25 mL。然后各组大鼠从试验的d 4到d 8进行不同的预处理，即每日分别灌服蒸馏水、维拉帕米(Ver)、低剂量和高剂量的TMP。d 9时各组大鼠单次合用CsA(10 mg·kg^-1)和上述的各种化合物后，按d 1的时间点采样。用HPLC法测定全血中CsA的浓度，计算其主要药代动力学参数并进行统计学分析。结果合用蒸馏水组的CsA药代动力学参数前后无显著性差异；Ver预处理并合用后，CsA的AUC^{0-48 h}和C_max均显著增加(P<0.01和P<0.05)，T^1/2β显著延长(P<0.05)，CL显著降低(P<0.05)，而T_max和V的变化无统计学差异。低剂量TMP预处理并合用后，CsA的AUC^{0-48 h}和C_max有增加的趋势，但无统计学差异，其余药代动力学参数的变化也无统计学的差异。高剂量TMP预处理并合用后，CsA的AUC^{0-48 h}和C_max均有显著的增加(P<0.01)，但其他药代动力学参数的变化无统计学差异。结论高剂量的TMP能显著提高CsA的灌服生物利用度，但对CsA的体内消除过程几乎没有影响。

The effect of tetramethylpyrazine on the pharmacokinetics of intragastrically administered cyclosporine A in rats

AIM: To investigate the possible effect of tetramethylpyrazine (TMP), an active ingredient of a commonly used Chinese herb, on the pharmacokinetics of cyclosporine A (CsA) by intragastric administration in rats. METHODS: Forty male Sprague-Dawley rats were equally divided into four groups by randomized block design according to weight. On the first day, after each fasting rat was intragastrically administered CsA (10 mg x kg(-1)), blood samples (0.2 - 0.25 mL) were collected from the tail vein at 0, 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h. From day 4 to day 8, each group began to undergo different pretreatments with intragastric administration of water, verapamil (Ver), low and high dose TMP, separately. On day 9, each group intragastrically co-administered CsA (10 mg x kg(-1)) and different pretreatment compounds mentioned above, then blood samples were collected according to the schedule of the first day. The whole blood concentration of CsA was determined by HPLC. Main pharmacokinetic parameters were calculated and compared by statistic analysis. RESULTS: In the group of water pretreated and co-administrated with CsA, no significantly different pharmacokinetic parameters of CsA were found. After Ver pretreatment and co-administration with CsA, AUC(0-48 h) and C(max) were increased significantly (P < 0.01 and P < 0.05); T(1/2) beta and CL were markedly prolonged and decreased (P < 0.05); T(max) and V were not apparently influenced. After low dose TMP pretreatment and co-administration with CsA, there was no significant difference in the pharmacokinetic parameters of CsA, in spite of the increasing trends of AUC(0-48 h) and C(max). After high dose TMP pretreatment and co-administration with CsA, AUC(0-48 h) and C(max) of CsA were increased significantly (P < 0.01), but there was no significant change in other parameters. CONCLUSION: It was indicated that the high dose of TMP could apparently increase the intragastric absorption extent of CsA, while almost had no effect on its elimination process.