Lubiprostone

Biological Activity

Lubiprostone (Amitiza) is a gastrointestinal agent used for the treatment of idiopathic chronic constipation. It is a bicyclic fatty acid (more precisely, prostaglandin E1) derivative that acts by specifically activating ClC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements (SBM).

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

A randomized, placebo-controlled trial of lubiprostone for opioid-induced constipation in chronic noncancer pain.
Jamal MM, et al. Am J Gastroenterol. 2015 May;110(5):725-32. PMID: 25916220.

A randomized study of lubiprostone for opioid-induced constipation in patients with chronic noncancer pain.
Cryer B, et al. Pain Med. 2014 Nov;15(11):1825-34. PMID: 24716835.