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| Pronunciation | Viberzi (/vaɪˈbɜːrzi/vy-BUR-zee |
| Trade names | Viberzi, Truberzi |
| Other names | JNJ-27018966 |
| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Protein binding | 81% |
| Eliminationhalf-life | 3.7–6 hours |
| Excretion | 82.2% (feces), <1% (urine)[2] |
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| Chemical and physical data | |
| Formula | C32H35N5O5 |
| Molar mass | 569.662 g·mol−1 |
| 3D model (JSmol) | |
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Eluxadoline, sold under the brand namesViberzi andTruberzi,[3] is a medication takenby mouth for the treatment ofdiarrhea andabdominal pain in individuals with diarrhea-predominantirritable bowel syndrome (IBS-D).[4] It was approved for use in the United States in 2015.[5] Thedrug originated fromJanssen Pharmaceutica and was developed byActavis.
This drug is contraindicated in case of having:
Common adverse effects are constipation and nausea, but rates of discontinuation due to constipation were low for both eluxadoline andplacebo. Rare adverse effects:fatigue,bronchitis,viral gastroenteritis.Rare serious adverse effects includepancreatitis with a general incidence of 0.3%: higher incidence with 100 mg dose (0.3%) than with 75 mg dose (0.2%).[7] The risk is even greater in those who do not have agallbladder and the medication is not recommended in this group.[8]
In March 2017, theU.S. Food and Drug Administration issued a safety alert for eluxadoline concerning an increased risk of serious pancreatitis in patients without a gallbladder.[9] An FDA review found that in such patients, spasm of thesphincter of Oddi may lead to severe pancreatitis.[10] The FDA reported that in some cases symptoms have occurred with just one or two doses at the recommended dosage for patients without a gallbladder (75 mg).[10] Of two deaths associated with eluxadoline reported up to February 2017, both occurred in patients without a gallbladder.[9]
Elevated concentrations of eluxadoline were observed with co-administration of inhibitors of the transporter proteinOATP1B1, such asciclosporin,gemfibrozil, certainantiretrovirals,rifampicin, andeltrombopag.[medical citation needed]
Concurrent use of other drugs that cause constipation, such asopioids,alosetron,anticholinergics, andbismuth subsalicylate, is not preferred.[11]
Eluxadoline increases the concentrations of drugs which are OATP1B1 andBCRP substrates.[medical citation needed] Co-administration of eluxadoline withrosuvastatin may increase the risk ofrhabdomyolysis.[2]
Eluxadoline is aμ- andκ-opioid receptoragonist andδ-opioid receptorantagonist[12] that acts locally in theenteric nervous system, possibly decreasing adverse effects on thecentral nervous system.[13][14]
In thein vitro studies, eluxadoline was found to be transported by OAT3 (SLC22A8), OATP1B1 (SLCO1B1), and BSEP (ABCB11) at the highest concentrations tested (400 ng/ml, which is 162-fold larger than the observed Cmax of the highest therapeutic dose of 100 mg). However, it wasnot to be transported by OCT1POU2F1, OAT1 (organic anion transporter 1), OCT2, OATP1B3 (SLCO1B3), P-gp (P-glycoprotein), or BCRP (ABCG2).
Multidrug resistance-associated protein 2 (MRP2)-vesicular accumulation of eluxadoline was observed, indicating that the drug is a substrate of MRP2. Eluxadoline was not found to inhibit BCRP-, BSEP-, MRP2-, OCT1-, OCT2-, OAT1-, OAT3-, or OATP1B3-mediated transport of probe substrates but inhibited the transport of probe substrates of OATP1B1 and P-gp. In thein vitro studies, it was observed that eluxadoline is anin vivo substrate of OATP1B1, OAT3, and MRP2. Finally, no inhibition or induction ofcytochrome P450 enzymes was observed.[15]
Following a 100 mg dose of eluxadoline, theCmax was about 2 to 4 ng/ml andAUC was 12 to 22 ng.h/ml. Eluxadoline has linearpharmacokinetics with no accumulation upon repeated twice daily dosing. Taking eluxadoline with high fat meal decreased the Cmax by 50% and AUC by 60%.[2]
The synthesis of eluxadoline was published in 2006.[16]
