Zhi J, Melia A T, Koss-Twardy S G, Min B, Guerciolini R, Freundlich N L, Milla G, Patel I H
Department of Clinical Pharmacokinetics, Hoffmann-La Roche, Inc., Nutley, NJ 07110-1199, USA.
J Clin Pharmacol. 1995 May;35(5):521-5. doi: 10.1002/j.1552-4604.1995.tb04098.x.
To assess the influence of orlistat on the pharmacokinetics and pharmacodynamics (the blood glucose-lowering effect) of glyburide, an open-label, placebo-controlled, randomized, two-way crossover study was done in 12 healthy male volunteers. Each subject received single 5-mg oral doses of glyburide (Micronase; The Upjohn Company, Kalamazoo, MI) on the fifth day of treatment with placebo (treatment A) and 80-mg orlistat (treatment B) three times a day for 4 1/3 days; the two treatments were separated by a five-day washout period. Serial blood samples were collected before and at appropriate intervals after each glyburide dose to determine plasma concentrations and blood glucose levels. Values of Cmax and AUC of glyburide showed an equality of the two treatments by the analysis of variance. There was an apparent correlation between blood glucose level and the logarithm of plasma glyburide concentration; this relationship appeared to not be altered when glyburide was administered with orlistat. In conclusion, orlistat administered at doses of 80-mg three times daily does not significantly alter the pharmacokinetics and blood glucose-lowering effect of a single 5-mg oral dose of glyburide in healthy volunteers.
为评估奥利司他对格列本脲药代动力学及药效学（降血糖作用）的影响，对12名健康男性志愿者进行了一项开放标签、安慰剂对照、随机、双向交叉研究。每位受试者在接受安慰剂治疗（治疗A）的第5天和每天3次服用80毫克奥利司他（治疗B），共4又1/3天的情况下，单次口服5毫克格列本脲（美吡达；美国普强公司，密歇根州卡拉马祖）；两种治疗之间有5天的洗脱期。在每次格列本脲给药前及给药后的适当时间间隔采集系列血样，以测定血浆浓度和血糖水平。通过方差分析，格列本脲的Cmax和AUC值显示两种治疗效果相当。血糖水平与血浆格列本脲浓度的对数之间存在明显相关性；当格列本脲与奥利司他合用时，这种关系似乎未改变。总之，在健康志愿者中，每日3次服用80毫克剂量的奥利司他不会显著改变单次口服5毫克格列本脲的药代动力学及降血糖作用。
