Press A G, Ewe K, Schmidt J, Junge H
1st Medical Clinic, Johannes-Gutenberg University, Mainz, FRG.
Eur J Clin Pharmacol. 1991;41(3):239-43. doi: 10.1007/BF00315436.
Jejunal perfusion was performed in 12 healthy volunteers to evaluate the dose dependent effects of loperamide on intestinal absorption, stimulated secretion and transit. In 6 volunteers intestinal perfusion of the jejunal segment with isotonic NaCl solution was followed by addition of loperamide in increasing doses (2-8 mg.l-1). The volunteers were pretreated with 1 mg.l-1 prostaglandin E2 (PgE2) in the perfusate before addition of 4 mg.l-1 loperamide. Phenolsulphonphtalein (PSP) boluses (2 ml) were given to measure mean transit time (MTT). Loperamide 2 mg.l-1 converted the minor secretion after perfusion with the standard solution (water -145 ml.min-1, Na -0.09 and Cl -0.04 mmol.min-1) to absorption (water 0.93 ml.min-1, Na 0.23, Cl 0.25 mmol.min-1) within 15 min. Higher doses of loperamide did not increase absorption. The addition of PgE2 induced net secretion of water (-4.48 ml.min-1) and electrolytes (Na -0.57, Cl -0.51 mmol.min-1). Loperamide 4 mg.l-1 significantly diminished the PgE2-induced net secretion by approximately 50%. Loperamide dose dependently increased the MTT from 6 (2 mg.l-1) to 13.3 min (8 mg.l-1). MTT was still delayed 60 min after a wash out period (10.5 min). It is concluded that loperamide had a dual effect or intestinal activities stimulating absorption and prolonging intestinal transit time with rising doses.
对12名健康志愿者进行空肠灌注，以评估洛哌丁胺对肠道吸收、刺激分泌和转运的剂量依赖性影响。在6名志愿者中，先用等渗氯化钠溶液对空肠段进行肠道灌注，然后添加递增剂量（2 - 8 mg·l⁻¹）的洛哌丁胺。在添加4 mg·l⁻¹洛哌丁胺之前，先在灌注液中用1 mg·l⁻¹前列腺素E2（PgE2）对志愿者进行预处理。给予酚磺酞（PSP）推注（2 ml）以测量平均转运时间（MTT）。2 mg·l⁻¹的洛哌丁胺在15分钟内将灌注标准溶液（水 - 145 ml·min⁻¹，钠 - 0.09和氯 - 0.04 mmol·min⁻¹）后的轻微分泌转变为吸收（水0.93 ml·min⁻¹，钠0.23，氯0.25 mmol·min⁻¹）。更高剂量的洛哌丁胺并未增加吸收。添加PgE2会引起水（-4.48 ml·min⁻¹）和电解质（钠 - 0.57，氯 - 0.51 mmol·min⁻¹）的净分泌。4 mg·l⁻¹的洛哌丁胺可使PgE2诱导的净分泌显著减少约50%。洛哌丁胺剂量依赖性地将MTT从6分钟（2 mg·l⁻¹）增加到13.3分钟（8 mg·l⁻¹）。冲洗期（10.5分钟）后60分钟，MTT仍被延迟。结论是，随着剂量增加，洛哌丁胺对肠道活动具有双重作用，即刺激吸收和延长肠道转运时间。
