Indiana University School of Medicine, Indianapolis, IN, USA.
Ann Surg. 2013 Aug;258(2):262-9. doi: 10.1097/SLA.0b013e31827a0e82.
We conducted a pharmacokinetic (PK) study and a pharmacodynamic (PD) study to assess whether Roux-en-Y gastric bypass (RYGB) surgery is associated with significant changes to PK and PD of oral medications.
The effect of RYGB on oral drug disposition is not well understood.
An oral cocktail of probe drugs for major drug-metabolizing enzymes (caffeine, tolbutamide, omeprazole, dextromethorphan, and oral and intravenous midazolam) was administered to 18 RYGB recipients and 18 controls. Timed blood and urine samples were obtained for PK analyses. Forty mg of oral furosemide was administered to 13 RYGB recipients and 14 controls, and urine and blood samples were collected for assessing furosemidePK, and urine volume and urine sodium excretion for PD analyses.
Compared with controls, the RYGB group had significantly lower time to maximum plasma concentration (tmax) for caffeine (0.58 ± 0.5 vs 2.1 ± 2.2 hours, P < 0.0001), tolbutamide (1.4 ± 1.8 vs 2.1 ± 2.2 hours, P = 0.0001), omeprazole (1.1 ± 1.1 vs 4.4 ± 1.3 hours, P < 0.0001), and oral midazolam (0.5 ± 0.2 vs 0.7 ± 0.4 hours, P < 0.01). However, maximum plasma concentration, half-life, area under the curve, and oral bioavailability were not different. Compared with controls, the RYGB group had brisk natriuresis, with significantly lower tmax for urine sodium (1.3 ± 0.5 vs 3.1 ± 2.3 hours, P < 0.02) and correspondingly lower tmax for furosemide (1.8 ± 0.3 vs 4.2 ± 1.2 hours, P = 0.006). However, 6-hour urine sodium and 6-hour urine volume were not different between the two groups.
RYGB recipients have significantly shorter tmax for the studied orally administered medications, but otherwise no other significant changes in PK were reported.
我们进行了一项药代动力学（PK）研究和一项药效学（PD）研究，以评估 Roux-en-Y 胃旁路（RYGB）手术是否与口服药物的 PK 和 PD 显著变化相关。
RYGB 对口服药物处置的影响尚不清楚。
给 18 例 RYGB 受者和 18 例对照者服用主要药物代谢酶（咖啡因、甲苯磺丁脲、奥美拉唑、右美沙芬、口服和静脉注射咪达唑仑）的口服鸡尾酒探针药物。进行 PK 分析时，采集定时血样和尿样。给 13 例 RYGB 受者和 14 例对照者服用 40mg 呋塞米，收集尿样和血样进行呋塞米 PK 分析，以及尿样体积和尿钠排泄进行 PD 分析。
与对照组相比，RYGB 组的咖啡因（0.58±0.5 比 2.1±2.2 小时，P<0.0001）、甲苯磺丁脲（1.4±1.8 比 2.1±2.2 小时，P=0.0001）、奥美拉唑（1.1±1.1 比 4.4±1.3 小时，P<0.0001）和口服咪达唑仑（0.5±0.2 比 0.7±0.4 小时，P<0.01）的达峰时间（tmax）显著缩短。但最大血浆浓度、半衰期、曲线下面积和口服生物利用度无差异。与对照组相比，RYGB 组钠排泄迅速，尿钠 tmax 明显降低（1.3±0.5 比 3.1±2.3 小时，P<0.02），相应地呋塞米 tmax 也降低（1.8±0.3 比 4.2±1.2 小时，P=0.006）。但两组间 6 小时尿钠和 6 小时尿量无差异。
RYGB 受者口服药物的 tmax 明显缩短，但 PK 无其他显著变化。
