Guentert T W, Defoin R, Mosberg H
F. Hoffmann-La Roche & Co. Ltd., Basel, Switzerland.
Eur J Clin Pharmacol. 1988;34(3):283-9. doi: 10.1007/BF00540957.
We have studied the influence of multiple oral doses of cholestyramine on the single dose pharmacokinetics of tenoxicam and piroxicam in eight healthy young volunteers. Each subject received on two occasions single intravenous injections of 20 mg tenoxicam and on another two occasions single oral doses of 20 mg piroxicam. Both medications were followed by multiple oral doses of either cholestyramine or plain water (placebo). Compared with placebo cholestyramine accelerated the elimination of both drugs. The average values of half-lives were reduced (tenoxicam: 31.9 h vs 67.4 h; piroxicam: 28.1 h vs 46.8 h) due to increases in clearance. Cholestyramine-mediated enhancement of drug elimination was most pronounced in the subjects with a comparatively low baseline drug clearance. Thus, intersubject variability in clearance was smaller when the drug administrations were followed by the anion-exchange resin. The twofold acceleration of tenoxicam elimination in the present study in man contrasts with a much larger effect (five-fold) seen in experiments with dogs. This points to a much easier access of unchanged tenoxicam to the intestinal lumen in the dogs than in man. Comparing the pharmacokinetics of tenoxicam and piroxicam in the same volunteers revealed a high degree of correlation in clearance and half-lives and similar intersubject variabilities in mean kinetic variables.
我们研究了多次口服考来烯胺对8名健康年轻志愿者单次服用替诺昔康和吡罗昔康药代动力学的影响。每位受试者接受两次20mg替诺昔康的单次静脉注射，以及另外两次20mg吡罗昔康的单次口服给药。两种药物给药后均多次口服考来烯胺或纯水（安慰剂）。与安慰剂相比，考来烯胺加速了两种药物的消除。由于清除率增加，半衰期的平均值降低（替诺昔康：31.9小时对67.4小时；吡罗昔康：28.1小时对46.8小时）。考来烯胺介导的药物消除增强在基线药物清除率相对较低的受试者中最为明显。因此，当药物给药后使用阴离子交换树脂时，受试者间清除率的变异性较小。本研究中人类受试者替诺昔康消除的两倍加速与犬实验中观察到的更大效应（五倍）形成对比。这表明在犬中未变化的替诺昔康比在人类中更容易进入肠腔。在相同志愿者中比较替诺昔康和吡罗昔康的药代动力学发现，清除率和半衰期高度相关，平均动力学变量的受试者间变异性相似。
