Constipation lubiprostone

As discussed previously, lubiprostone is a prostanoic acid derivative that stimulates the type 2 chloride channel (CIC-2) in the small intestine and is used in the treatment of chronic constipation. Lubiprostone recently was approved for the treatment of women with IBS with predominant constipation. Its efficacy for men with IBS is unproven. 

The approved dose for IBS is 8 meg twice daily (compared with 24 meg twice daily for chronic constipation). Lubiprostone has not been compared with other less expensive laxatives (eg, milk of magnesia). Lubiprostone is listed as category C for pregnancy and should be avoided in women of childbearing age. 

Lubiprostone (Amitiza), a bicyclic acid oral agent, is approved for treatment of chronic idiopathic constipation in adults. It has not been studied in children. Lubiprostone acts locally on intestinal chloride channels and increases intestinal fluid secretion, resulting in increased intestinal motility and thereby increasing the passage of stool.6... 

Lubiprostone is a chloride channel activator that acts locally on the gut to accelerate genitourinary transit time and delay gastric emptying. It is approved for chronic idiopathic constipation in adults. The dose is 24 mg capsule twice daily with food. Lubiprostone may cause headache, diarrhea, and nausea. 

Lubiprostone (Amitiza) [Laxative] Uses Chronic idiopathic constipation in adults Action Selective Cl channel activator Dose Adults. 24 meg PO bid w/ food Contra Mechanical GI obst Caution [C, /-] Severe D, severe renal or mod-severe hepatic impair Disp Gel, caps meg SE N, HA, D, GI distention, abd pain EMS Monitor for signs of electrolyte disturbances and h5rpovolemia d/t D OD May cause severe D, hypovolemia, and abd pain/cramps give IV fluids Lutropin Alfa (Luveris) [Hormone] Uses Inf ility Action Recombinant LH Dose 75 Units SQ w/ 75—150 Units FSH, 2 s arate inj max 14 d Caution [X, /M] Contra Primary ovarian failure, uncontrolled thyroid/adrenal dysfxn, intracranial lesion, AUB, hormone-dqjendent GU tumor, ovarian cyst, PRG Disp Inj SE HA, N, ovarian h5rpCTstimulation synd, breast pain, ovarian cysts T risk of multiple births EMS None OD Unlikely to cause life-threatening Sxs... 

Lubiprostone is a novel agent, currently in clinical phase III for the treatment of constipation. This 16,16-difluoro-15-ketoprostaglandine potently activates intestinal Ch channels without altering Na+ and K+ ones. The difluoromethylk-etone is in equilibrium with the bicyclic hemiketal form, and the latter is predominant in the absence of water (Fig. 71) [166],... 

L.A. Sorbera, J. Castaner, N.E. Mealy, Lubiprostone. Treatment of constipation, treatment of irritable bowel syndrome, treatment of postoperative ileus, CIC-2 channel activator, Drugs Fut. 29 (2004) 336-342. 

Lubiprostone has used as a novel PG compound for an oral treatment of constipation with a unique action directed to the target tissue, although it has low systemic availability following oral administration. It activates a locally acting chloride channel, which is a normal constituent of the apical membrane of the human intestine, and enhances a chloride-rich intestinal fluid secretion without altering sodium and potassium concentration in the serum. In fasted rats administered doses of 1, 10, or lOOpg/kg of the compound, dose-dependent increases in the concentration of chloride ions in the bowel were detected, indicating that the compound opens chloride channels and promotes chloride ion transport in vivo [45]. 

The standard pharmacokinetic parameters of the compound such as a half-life or bioavailability cannot be reliably calculated, because the concentrations in plasma are below lOpg/mL. As analogously expected from the results on the shift in keto-alcohol equilibrium of 16,16-difluoro-PGE2, it is rapidly metabolized by C-15 reduction mediated by the ubiquitously expressed carbonyl reductase. The metabolism followed by jS-oxidation and co-oxidation forms a mixture of a and fi epimers at the 15-hydroxy moiety as a sole measurable metabolite [46], In 2006, the US Food and Drug Administration approved the drug application for an oral treatment of chronic idiopathic constipation in adults, estimating that 4-5 million Americans are affected. Lubiprostone has also completed a phase II trial in constipation-predominant irritable bowel syndrome, and has been further evaluated for other bowel dysfunctions. 

Lubiprostone is a prostanoic acid derivative labeled for use in chronic constipation and irritable bowel syndrome (IBS) with predominant constipation. It acts by stimulating... 

Chloride channel activator Lubiprostone (see above) useful in constipation-predominant IBS in women ... 

Johanson JF et al Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-active type-2 chloride channel activator, in patients with chronic constipation. Am J Gastroenterol 2008 103 170. [PMID 17916109]... 

A PGE related compound, lubiprostone (23) displays a quite different spectrum of activity. This compound has been recently approved for treatment of chronic constipation and is being investigated for its effect on constipation-predominant irritable bowel syndrome. It has been ascertained that the drug interacts with specific ion channels in the G1 tract causing increased fluid output into the lumen. Starting material for the synthesis (13) comprises yet another variant on the Corey lactone. Condensation... 

Lubiprostone is a water-insoluble heptanoic acid derivative used in the treatment of chronic idiopathic constipation in adults, and is solubilized in medium-chain triglyceride in 24 pg Amitiza soft gelatin capsules. The dose of lubiprostone is 24 pg (one capsule) twice daily with food. Amitiza should be stored at controlled room temperature and was approved in the USA in 2006. 

Open-label studies An open-label extension study assessed the long-term safety, tolerability and efficacy of lubiprostone in 520 patients with constipation-predominant irritable bowel syndrome. Patients were orally administered lubiprostone (8 meg) twice daily for 36 weeks. The most common adverse events were diarrhoea (11%), nausea (11%), urinary tract infection (9%), sinusitis (9%) and abdominal distention (5.8%). No serious adverse events were considered as being treatment related. Seventeen patients discontinued lubiprostone due to a treatment-related adverse event, of which diarrhoea and nausea accoxmted for 1.2% and 0.6%, respectively [9. ... 

Ghey WD, Drossman DA, Johanson JF, Scott C, Panas RM, Ueno R. Safety and patient outcomes with lubiprostone for up to 52 weeks in patients with irritable bowel syndrome with constipation Aliment Pharmacol Ther 2012 35 587-99. 

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