Biological Activity

• DescriptionAs 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 ^[4]. 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) ^[5].}

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

• Clinical Study

• NCT Number	Condition or disease	Phase	Recruitment Status	Estimated Study Completion Date	Locations
  NCT00953017	-	-	Completed	-	-
  NCT03720613	-	-	Not yet recruiting	November 1, 2025	-
  NCT00577499	-	-	Terminated(Recruitment was sub... more >>optimal) Collapse <<	-	-

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• References

• [1] Bijvelds MJ, Bot AG, et al. Activation of intestinal Cl- secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator. Gastroenterology. 2009 Sep;137(3):976-85.

  [2] Bassil AK, Borman RA, et al. Activation of prostaglandin EP receptors by lubiprostone in rat and human stomach and colon. Br J Pharmacol. 2008 May;154(1):126-35.

  [3] RU 0211

  [4] Ao M, Venkatasubramanian J, Boonkaewwan C, Ganesan N, Syed A, Benya RV, Rao MC. Lubiprostone activates Cl- secretion via cAMP signaling and increases membrane CFTR in the human colon carcinoma cell line, T84. Dig Dis Sci. 2011 Feb;56(2):339-51. doi: 10.1007/s10620-010-1495-8. Epub 2010 Dec 8. PMID: 21140215.

  [5] Bassil AK, Borman RA, Jarvie EM, McArthur-Wilson RJ, Thangiah R, Sung EZ, Lee K, Sanger GJ. Activation of prostaglandin EP receptors by lubiprostone in rat and human stomach and colon. Br J Pharmacol. 2008 May;154(1):126-35. doi: 10.1038/bjp.2008.84. Epub 2008 Mar 10. PMID: 18332851; PMCID: PMC2438971.

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