Effect of protease inhibitors (indinavir and ritonavir) on the pharmacokinetics of gliclazide in rabbits

Research and reports in endocrine disorders Pub Date : 2011-01-20 DOI:10.2147/RRED.S16496

K. Kumar, S. Mastan

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引用次数: 2

Abstract

The objective of this study was to investigate the effect of protease inhibitors (indinavir and ritonavir) on the pharmacokinetics of gliclazide in rabbits and to evaluate the mechanism of interaction of the combination. Studies in rabbits were conducted with oral doses of gliclazide, selected protease inhibitor, and their combination with a 1-week washout period between each treatment (single dose followed by multiple dose treatment). Blood samples were collected at regular time intervals by marginal ear vein puncture and serum gliclazide levels were analyzed by high-pressure liquid chromatography. Pharmacokinetic analysis was performed by noncompartmental analysis using WinNonlin Software. In combination, ritonavir significantly increased serum gliclazide levels and altered the pharmacokinetic parameters of gliclazide in rabbits while indinavir had no significant effect. The percentage increase of serum gliclazide level was 22.34% and 27.78% following single-dose and multiple-dose treatment of ritonavir, respectively. The interaction of ritonavir with gliclazide is pharmacokinetic at a metabolic level (by CYP3A4 inhibition) in normal rabbits, while the interaction of indinavir with gliclazide is pharmacodynamic, which needs dose adjustment, and care should be taken when these

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蛋白酶抑制剂(茚那韦和利托那韦)对格列齐特在家兔体内药动学的影响

本研究的目的是研究蛋白酶抑制剂(茚地那韦和利托那韦)对格列齐特在家兔体内药动学的影响，并评价两者联合作用的机制。在家兔实验中，采用口服剂量的格列齐特(选定的蛋白酶抑制剂)及其联合用药，每次治疗之间有1周的洗脱期(单次给药后多次给药)。采用耳缘静脉穿刺法定期采血，采用高压液相色谱法分析血清格列齐特水平。采用WinNonlin软件进行药代动力学分析。利托那韦联合用药可显著提高家兔血清格列齐特水平，改变格列齐特药动学参数，而茚地那韦对其无显著影响。利托那韦单次给药和多次给药后血清格列齐特水平分别升高22.34%和27.78%。利托那韦与格列齐特的相互作用在正常家兔体内是代谢水平的药代动力学(通过抑制CYP3A4)，而因地那韦与格列齐特的相互作用是药理学，需要调整剂量，注意

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Research and reports in endocrine disorders

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