Slanar O, Aubrecht J, Perlík F
First Medical Department, Clinical Pharmacology Unit, General Teaching Hospital, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Physiol Res. 2002;51(4):413-6.
Portal-systemic shunting is an important circulatory abnormality in patients with liver cirrhosis. Glyceryl trinitrate (GTN) that is normally subject to first pass elimination, may exhibit higher bioavailability in these patients. This study compares the pharmacodynamic effects of GTN after peroral and sublingual administration for noninvasive assessment of shunting. Six control subjects and 15 patients with cirrhosis were studied after oral and sublingual application of 0.5 mg of GTN. Liver cirrhosis was complicated by portal hypertension in 7 of the patients and 4 patients had surgically implanted portocaval anastomosis. Digital plethysmography, which is highly sensitive and is essentially noninvasive in nature, was used to assess and compare the pharmacodynamic effects of GTN. The following values of the ratio of areas under the pharmacodynamic effects/time curve were obtained: 0.08 +/- 0.06 in healthy subjects, 0.52 +/- 0.21 in patients with uncomplicated cirrhosis, 0.99 +/- 0.34 in patients with portal hypertension and 1.24 +/- 0.43 in patients with portal-systemic shunts. We conclude that increased bioavailability of GTN reflects portal-systemic shunting and might be used providing that the pharmacodynamic data reflect both pharmacokinetic variability and the pharmacokinetic-pharmacodynamic interrelations.
门体分流是肝硬化患者重要的循环异常。通常会经历首过消除的硝酸甘油（GTN），在这些患者中可能会表现出更高的生物利用度。本研究比较了口服和舌下含服GTN后的药效学效应，以对分流进行无创评估。在6名对照受试者和15名肝硬化患者口服和舌下应用0.5 mg GTN后进行了研究。7名患者的肝硬化合并门静脉高压，4名患者进行了手术植入的门腔静脉吻合术。数字体积描记法高度敏感且本质上无创，用于评估和比较GTN的药效学效应。获得了以下药效学效应/时间曲线下面积比值：健康受试者为0.08±0.06，无并发症肝硬化患者为0.52±0.21，门静脉高压患者为0.99±0.34，门体分流患者为1.24±0.43。我们得出结论，GTN生物利用度的增加反映了门体分流，并且如果药效学数据反映了药代动力学变异性和药代动力学-药效学相互关系，可能会被应用。
