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目的:研究Wistar大鼠单次灌服辛伐他汀后体内药代动力学的性别差异。方法:利用高效液相色谱方法检测大鼠血浆中辛伐他汀浓度,采用非房室模型法计算各自药动学参数。结果:雌、雄大鼠体内Cmax分别为(144.66±22.31)ng·mL~(-1)和(165.91±52.50)ng·mL~(-1);t_(1/2)分别为(4.74±1.19)h和(14.98±6.64)h;AUC_(0-10)分别为(0.990±0.19)μg.h·mL~(-1)和(0.726±0.15)μg·h·mL~(-1);AUC0-∞分别为(1.62±0.47)μg·h·mL~(-1)和(2.19±0.62)μg·h·mL~(-1);MRT分别为(9.69±1.60)h和(23.08±8.89)h,经t-检验,雌、雄大鼠主要药动学参数t_(1/2)、AUC_(0-10)、MRT均有统计学显著性差异(p<0.01)。结论:辛伐他汀在大鼠体内的药代动力学存在明显的性别差异,辛伐他汀在雌性大鼠体内代谢较快。
OBJECTIVE: To study the in vivo pharmacokinetics of Wistar rats after single administration of simvastatin. Methods: Plasma concentrations of simvastatin in rat plasma were determined by HPLC. Pharmacokinetic parameters were calculated by non-compartmental model. Results: The C max of male and female rats were (144.66 ± 22.31) ng · mL -1 and (165.91 ± 52.50) ng · mL -1, respectively; t 1/2 was 4.74 ± 1.19 ) and (14.98 ± 6.64) h, respectively. The AUC_ (0-10) were (0.990 ± 0.19) μg.h · mL -1 and (0.726 ± 0.15) μg · h · mL -1, respectively. AUC0-∞ were (1.62 ± 0.47) μg · h · mL -1 and (2.19 ± 0.62) μg · h · mL -1, respectively; MRT was (9.69 ± 1.60) h and (23.08 ± 8.89) h. The main pharmacokinetic parameters t_ (1/2), AUC_ (0-10) and MRT in female and male rats were statistically significant difference (p <0.01) by t-test. Conclusion: There is a significant gender difference in the pharmacokinetics of simvastatin in rats. Simvastatin is metabolized rapidly in female rats.