Effect of a Single Gemfibrozil Dose on the Pharmacokinetics of Rosuvastatin in Bile and Plasma in Healthy Volunteers
Effect of a Single Gemfibrozil Dose on the Pharmacokinetics of Rosuvastatin in Bile and Plasma in Healthy Volunteers
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DOI：
10.1177/0091270009357432
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发表时间：
2010-09-01
影响因子：
2.9
通讯作者：
Lennernas, Hans
中科院分区：
文献类型：
--
作者：
Bergman, Ebba;Matsson, Elin M.;Lennernas, Hans
在8名健康志愿者中，使用位于远端空肠-近端空肠的多通道导管，研究了吉非罗齐（600 mg）单次空肠内给药对瑞舒伐他汀（20 mg）单次空肠内给药的血浆药代动力学和胆汁排泄的影响。每20分钟采集一次胆汁和血浆样本，持续200分钟，并采集额外的血浆样本，持续长达48小时。吉非罗齐不影响瑞舒伐他汀的生物利用度，尽管它使最初200分钟内的表观吸收相（AUC（血浆，200分钟））增加了1.56倍（95%置信区间，1.14-2.15）。与既往报告中吉非罗齐重复给药相比，该单次给药研究中的相互作用不太明显;然而，该相互作用与吉非罗齐的最高暴露量一致。本研究中相互作用仅为轻微的合理原因是吉非罗齐（及其代谢产物）的暴露量较低，表明吉非罗齐的总血浆浓度需要高于20 μ M才能影响瑞舒伐他汀的处置。本研究证明了监测抑制剂的血浆药代动力学的价值，而不仅仅是研究中的药物，以改善机制解释。
The effect of a single intrajejunal dose of gemfibrozil (600 mg) on the plasma pharmacokinetics and biliary excretion of a single intrajejunal dose of rosuvastatin (20 mg) was investigated by using a multichannel catheter positioned in the distal duodenum-proximal jejunum in 8 healthy volunteers. Bile and plasma samples were collected every 20 minutes for 200 minutes, with additional plasma samples being drawn for up to 48 hours. Gemfibrozil did not affect the bioavailability of rosuvastatin, although it increased the apparent absorption phase during the initial 200 minutes (AUC(plasma,200min)) by 1.56-fold (95% confidence interval, 1.14-2.15). The interaction was less pronounced in this single-dose study than in a previous report when gemfibrozil was administered repeatedly; nevertheless, the interaction coincided with the highest exposure to gemfibrozil. The plausible reason why the interaction in this investigation was only minor is the low exposure to gemfibrozil (and its metabolites), suggesting that the total plasma concentration of gemfibrozil needs to be above 20 mu M to affect the disposition of rosuvastatin. This study demonstrates the value of monitoring the plasma pharmacokinetics of the inhibitor, and not only the drug under investigation, to improve the mechanistic interpretation.