生物活性

• 描述As one of the nine members of the ClC family, ClC-2 (chloride channel type-2) is broadly expressed throughout the body, including the gastrointestinal tract. Lubiprostone, a possible ClC-2 channel opener indicated for the treatment of constipation, increases chloride ion transport and fluid secretion into the intestinal lumen. Lubiprostone (3 nM–10 μM) induced a concentration-dependent contraction of the longitudinal muscle, with a pEC_{50 of 7.0 and maximal effect of 95±3% of the response to 1 μM PGE2 (n=4). Lubiprostone also caused a concentration-dependent contraction of circular muscle preparations. In rat colon longitudinal muscle, lubiprostone (10 nM–10 μM) caused a muscle contraction (maximum at 10 μM; 140±74% of the response to 1 μM PGE2, n=4). In human proximal stomach longitudinal muscle, lubiprostone induced a concentration-dependent contraction with a pEC50 of 6.4±0.2 and maximal effect at 10 μM of 102±17% of the response to 1 μM PGE2 (n=3).}

• 动物研究
  剂量	Mice: 500 μg/kg/day[3] (p.o.) Rat: 0.1 mg/kg - 1 mg/kg[4] (p.o.)
  给药途径	p.o.
  动物药代数据	Animal Rats[5] Dogs[5] Dose 50 μg/kg 5 μg/kg Administration p.o. p.o. AUC0→24h 63.4 ng eq·h/ml 14.5 ± 2.2 ng eq.·h/ml AUC0→last 10.2 ng eq·h/ml 12.5 ± 1.9 ng eq.·h/ml T1/2 2.55 h t1/2α 1.12 ± 0.02 h t1/2β 2.48 ± 0.13 h Tmax 0.25 h 0.58 ± 0.14 h Cmax 10.60 ng eq/ml 6.31 ± 0.49 ng eq./ml AUC0→∞ 28.0 ng eq·h/ml 13.4 ± 1.9 ng eq.·h/ml