Porschen R, Pieper S, Bernhardt L, Schade B, Wienbeck M
Department of Gastroenterology, University of Düsseldorf.
Z Gastroenterol. 1988 Dec;26(12):755-61.
Studies in animals suggest that calcium channel blockers may influence gallbladder contraction. In order to study possible actions in man we examined by ultrasonography the effects of two dihydropyridine derivatives, i.e. nifedipine (20 mg p. o.) and BAY 1 8201 (100 mg p.o.) on ceruletide induced human gallbladder contraction in 9 healthy male volunteers in a randomized, double-blind, three fold crossover study (latin square design). Blood samples for the measurement of plasma drug concentrations were drawn before and at regular intervals up to 8 h after drug ingestion. Ceruletide decreased gallbladder volumes by 52.1 +/- 8.2% (mean +/- 1 SEM) after nifedipine, 53.1 +/- 8.1% after BAY 1 8201 and by 59.3 +/- 10.1% after placebo (NS). Peak plasma concentrations of 53.7 x/: 2.3 ng/ml (geometric mean x/: geometric standard deviation) and of 35.5 x/: 1.5 ng/ml were reached after oral application of nifedipine and BAY 1 8201, respectively. We conclude that human gallbladder contraction in response to ceruletide is not markedly influenced by dihydropyridine derivates in the dosages used in this study. The results reported here stress the importance of calcium released from intracellular stores for the contractility of smooth muscle in the human gallbladder.
动物研究表明，钙通道阻滞剂可能会影响胆囊收缩。为了研究其在人体中的可能作用，我们在9名健康男性志愿者中进行了一项随机、双盲、三交叉研究（拉丁方设计），通过超声检查两种二氢吡啶衍生物，即硝苯地平（口服20毫克）和BAY 1 8201（口服100毫克）对蛙皮素诱导的人体胆囊收缩的影响。在服药前及服药后直至8小时的规定间隔时间采集血样，以测定血浆药物浓度。服用硝苯地平后，蛙皮素使胆囊体积减少52.1±8.2%（平均值±1标准误）；服用BAY 1 8201后，减少53.1±8.1%；服用安慰剂后，减少59.3±10.1%（无显著性差异）。口服硝苯地平和BAY 1 8201后，血浆峰值浓度分别达到53.7×2.3纳克/毫升（几何平均值×几何标准差）和35.5×1.5纳克/毫升。我们得出结论，本研究中所用剂量的二氢吡啶衍生物对蛙皮素引起的人体胆囊收缩无明显影响。此处报告的结果强调了细胞内储存释放的钙对人体胆囊平滑肌收缩性的重要性。
