Gesquiere Ina, Hens Bart, Van der Schueren Bart, Mols Raf, de Hoon Jan, Lannoo Matthias, Matthys Christophe, Foulon Veerle, Augustijns Patrick
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Clinical and Experimental Endocrinology, KU Leuven and Department of Endocrinology, University Hospitals Leuven/KU Leuven, Leuven, Belgium.
Br J Clin Pharmacol. 2016 Nov;82(5):1325-1332. doi: 10.1111/bcp.13054. Epub 2016 Jul 25.
Roux-en-Y gastric bypass (RYGB) alters the anatomical structure of the gastrointestinal tract, which can result in alterations in drug disposition. The aim of the present study was to evaluate the oral disposition of two compounds belonging to the Biopharmaceutical Classification System Class II - fenofibrate (bile salt-dependent solubility) and posaconazole (gastric pH-dependent dissolution) - before and after RYGB in the same individuals.
A single-dose pharmacokinetic study with two model compounds - namely, 67 mg fenofibrate (Lipanthyl®) and 400 mg posaconazole (Noxafil®) - was performed in 12 volunteers pre- and post-RYGB. After oral administration, blood samples were collected at different time points up to 48 h after administration. Plasma concentrations were determined by high-performance liquid chromatography in order to calculate the area under the concentration-time curve up to 48 h (AUC ), the peak plasma concentration (C and the time to reach peak concentration (T ).
After administration of fenofibrate, no relevant differences in AUC , C and T between the pre- and postoperative setting were observed. The geometric mean of the ratio of AUC post/pre-RYGB for fenofibrate was 1.10 [95% confidence interval (CI) 0.87, 1.40; P = 0.40]. For posaconazole, an important decrease in AUC and C following RYGB was shown; the geometric mean of the AUC post/pre-RYGB ratio was 0.68 (95% CI 0.48, 0.96; P = 0.03) and the geometric mean of the C pre/post-RYGB ratio was 0.60 (95% CI 0.39, 0.94; P = 0.03). The decreased exposure of posaconazole could be explained by the increased gastric pH and accelerated gastric emptying of fluids post-RYGB. No difference for T was observed.
The disposition of fenofibrate was not altered after RYGB, whereas the oral disposition of posaconazole was significantly decreased following RYGB.
Roux-en-Y胃旁路术（RYGB）改变了胃肠道的解剖结构，这可能导致药物处置的改变。本研究的目的是评估在同一受试者中，RYGB术前和术后属于生物药剂学分类系统II类的两种化合物——非诺贝特（胆汁盐依赖性溶解度）和泊沙康唑（胃pH依赖性溶解）的口服处置情况。
对12名志愿者在RYGB术前和术后进行了两种模型化合物——即67毫克非诺贝特（力平之®）和400毫克泊沙康唑（诺科飞®）的单剂量药代动力学研究。口服给药后，在给药后长达48小时的不同时间点采集血样。通过高效液相色谱法测定血浆浓度，以计算至48小时的浓度-时间曲线下面积（AUC）、血浆峰浓度（C）和达峰时间（T）。
服用非诺贝特后，术前和术后的AUC、C和T未观察到相关差异。非诺贝特RYGB术后与术前AUC比值的几何均值为1.10 [95%置信区间（CI）为0.87, 1.40；P = 0.40]。对于泊沙康唑，RYGB术后AUC和C显著降低；RYGB术后与术前AUC比值的几何均值为0.68（95%CI为0.48, 0.96；P = 0.03），RYGB术后与术前C比值的几何均值为0.60（95%CI为0.39, 0.94；P = 0.03）。泊沙康唑暴露量降低可归因于RYGB术后胃pH值升高和胃内液体排空加速。T未观察到差异。
RYGB术后非诺贝特的处置未改变，而RYGB术后泊沙康唑的口服处置显著降低。
