硝酸布康唑栓的人体药代动力学
Pharmacokinetics of butoconazole nitrate suppositories in human
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摘要: 研究单次及多次阴道给药后硝酸布康唑栓在中国健康女性体内的药代动力学特征。12名健康女性受试者依次进行硝酸布康唑栓低(0.05 g)、高(0.1 g)剂量单次给药以及高剂量(0.1 g)连续给药3 d和连续给药5 d药代动力学试验。受试者单次阴道给予0.05和0.1 g受试制剂后，布康唑的cmax分别为(0.895 0±0.261 0)、(1.740±0.511)ng/mL，AUC0-96 h分别为(36.38±10.82)、(73.48±28.99)ng·h/mL，t1/2分别为(23.0±4.4)、(21.5±5.9)h。结果表明:布康唑在0.05~0.1 g剂量范围内呈线性药代动力学特征。受试者连续3 d给予硝酸布康唑栓后，布康唑的血药浓度波动度(DF)为(0.54±0.27)，累积常数Rcmax为(1.3±0.3)，RAUC0-τ为(1.4±0.3)。连续给药5 d后，布康唑的血药浓度DF为(0.64±0.25)，累积常数Rcmax为(1.4±0.3)，RAUC0-τ为(1.6±0.2)，在人体内的暴露量增加约60%。连续给药3 d与连续给药5 d的各项药动学参数均无显著性差异。Abstract: The aim of the study was to investigate the pharmacokinetics of butoconazole nitrate suppositories in healthy Chinese female volunteers after single and multiple-dose vaginal administration. 12 healthy Chinese female volunteers received single 0. 05 g, single 0. 1 g, multiple doses(0. 1 g per day, 3-day consecutive administration)and multiple doses(0. 1 g per day, 5-day consecutive administration)of butoconazole nitrate suppositories. For 0. 05 g and 0. 1 g single vaginal administration of butoconazole nitrate suppositories, the cmax were(0. 895 0±0. 261 0)and(1. 740±0. 511)ng/mL and the AUC0-96 h were(36. 38±10. 82)and(73. 48±28. 99)ng ·h/mL, respectively. In the range of 0. 05-0. 1 g, butoconazole demonstrated linear pharmacokinetics. In the multiple-dose study at 0. 1 g dose for 3 consecutive days, the degree of fluctuation(DF)was(0. 54±0. 27), and the accumulation parameters Rcmax and RAUC0-τ were(1. 3±0. 3)and(1. 4±0. 3), respectively. In the multiple-dose study at 0. 1 g dose for 5 consecutive days, the DF was(0. 64±0. 25), and the accumulation parameter Rcmax and RAUC were(1. 4±0. 3))and(1. 6±0. 2), respectively. An accumulation of 60% in AUC0-τ occurred after a multiple administration. The main pharmacokinetic parameters between 3-day consecutive administration and 5-day consecutive administration showed no significant difference.
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