Pharmacokinetic considerations for drugs that treat diarrhea-predominant irritable bowel syndrome: what’s new?

ABSTRACT

Introduction

Irritable bowel syndrome (IBS), which presents a significant healthcare and socioeconomic burden, is one of the main issues in the field of therapy. Hence, it is imperative to tackle this matter by evaluating the safety and efficacy of the available treatments and determining the ideal approach for each patient.

Areas Covered

We reviewed the pharmacokinetics and safety of pharmacologic interventions administered in diarrhea-predominant IBS (IBS-D) patients. PubMed, Google Scholar and the USFDA databases were searched up to November 2023 to include all updated information on eluxadoline, alosetron, and rifaximin.

Expert Opinion

The most effective way to treat IBS-D is to focus on managing the most common symptoms. However, healthcare providers face a challenge when it comes to identifying the right treatment for each patient, and the root cause of this is the diversity of IBS-D population. Studies have shown that there are differences in how men and women metabolize drugs, which may lead to gender-specific adverse reactions. Women tend to have higher drug concentrations in their bloodstream and take longer to eliminate them. Therefore, healthcare providers may need to reduce the dosage for female patients. Integrating IBS care into sustainable development efforts can indirectly contribute to achieving SDGs and promote health and well-being for all.

KEYWORDS:

• Diarrhea
• drug interactions
• eluxadoline
• irritable bowel syndrome
• metabolism
• pharmacokinetics
• SDG

Article highlights

• The duration of medication administration, safety, tolerability, and pharmacokinetics profiles must be considered when treating patients with IBS-D.

• Significant safety issues associated with IBS-D therapies include the risk of pancreatitis with eluxadoline and the potential for ischemic colitis, as well as the severe consequences of constipation with alosetron.

• Eluxadoline should not be used in patients with severe hepatic dysfunction, and a dose of 75 mg twice daily is recommended for moderate to severe renal dysfunction.

• Concurrent use of fluvoxamine can lead to a 6-fold increase in alosetron AUC and a 3-fold prolongation of its half-life, making it inadvisable to administer both drugs together.

• Post-marketing surveillance has reported alterations in the INR in patients concurrently administered rifaximin and warfarin. Close monitoring of the INR and prothrombin time is warranted.

• Finally, gender-specific adverse drug reactions may be more likely due to pharmacokinetic differences between males and females. Women in multiple trials had higher blood concentrations and longer elimination times.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. SM provides oncology drug consultancy to a pharmaceutical company. However, no conflicts of interest exist, and the author mentions this for transparency.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

This paper is the outcome of an in-house, financially non-supported study.

Additional information

Funding

This paper was not funded.