Genotype Stratified Pharmacokinetic Study of Montelukast

NCT01086527 | Completed Phase 1

• 2 other identifiers: 3788532-03215-005
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Leukotriene receptor antagonists (LTRAs) are frequently prescribed to reduce the symptoms associated with asthma. Singulair (montelukast), manufactured by Merck, is a popular LTRA, however its effectiveness varies greatly between individuals. We are interested in understanding why the effectiveness of Singulair varies so greatly. For an oral drug such as Singulair to be effective, the body must efficiently absorb it. We have found that blood levels of Singulair vary greatly between individuals, and we think that this variability is responsible for variability in response. Drug absorption occurs primarily in the intestine. Due to differences in the chemical properties of drugs, some drugs can be absorbed easily while other drugs require help from special proteins produced by the cells that line the intestine. These proteins, or transporters act like revolving doors to allow drugs to move from the intestine to the bloodstream. The activity of a transporter can be influenced by individual genetic variability. We think that adsorption of Singulair requires help from a transport protein called OATP2B1. We have found that a single common genetic change in this protein is associated with low plasma concentration of montelukast. In this proposal we will determine plasma levels of montelukast in individuals with two copies of this genetic change. We predict that these individuals will have roughly half the plasma level of montelukast as individuals with no copies of this genetic change. Eventually, what we learn from this work will allow doctors to quickly test individuals with asthma to determine how well they will absorb Singulair and possibly other LTRAs. Knowing this will allow the doctor to adjust the drug treatment on an individual basis to maximize benefit in the treatment of asthma.

Conditions

Asthma

Keywords

Pharmacogenetics; Singulair; montelukast; Leukotriene Antagonists; Anti-Asthmatic Agents; Intestinal Absorption; pharmacokinetics; absorption; biochemical transport; Membrane Transport Proteins

Outcome Measures

Primary Outcomes (1)

• AUC of montelukast

  Area under the concentration vs. time curve for the plasma concentration of montelukast.

  0-12 hours

Secondary Outcomes (1)

• Ke of montelukast

  0-12 hours

Study Arms (1)

SLCO2B1{NM_007256.2}:c.[935G>A] + [=]

EXPERIMENTAL

Individuals in this group will be homozygous for SLCO2B1{NM\_007256.2}:c.\[935G\>A\].

Drug: 10 mg tablet of montelukast (Singulair)

Interventions

10 mg tablet of montelukast (Singulair) DRUG

Fasting patients will take a single 10 mg tablet of montelukast with 240 ml of Gatorade. Eight blood samples will be drawn to assess the plasma concentration of montelukast over the subsequent 12 hours.

Also known as: Singulair

SLCO2B1{NM_007256.2}:c.[935G>A] + [=]

Eligibility Criteria

• Age: 7 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Individuals will be 7-35 years old.
• Individuals will be healthy or have doctor diagnosed asthma.
• Individuals 7-18 years old will have doctor diagnosed asthma.
• Individuals will have the (A/A) genotype at c.935.

You may not qualify if:

• Individuals must not be taking any oral medications except for ICS/or albuterol.
• Women must not be pregnant.

Sponsors & Collaborators

• Nemours Children's Clinic: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

Related Publications (2)

• Mougey EB, Feng H, Castro M, Irvin CG, Lima JJ. Absorption of montelukast is transporter mediated: a common variant of OATP2B1 is associated with reduced plasma concentrations and poor response. Pharmacogenet Genomics. 2009 Feb;19(2):129-38. doi: 10.1097/FPC.0b013e32831bd98c.

  PMID: 19151602 BACKGROUND

• Mougey EB, Lang JE, Wen X, Lima JJ. Effect of citrus juice and SLCO2B1 genotype on the pharmacokinetics of montelukast. J Clin Pharmacol. 2011 May;51(5):751-60. doi: 10.1177/0091270010374472. Epub 2010 Oct 25.

  PMID: 20974993 BACKGROUND

MeSH Terms

Conditions

Asthma

Interventions

montelukast

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Edward B Mougey, Ph.D.

  Nemours Children's Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Scientist

Study Record Dates

• First Submitted: March 11, 2010
• First Posted: March 15, 2010
• Study Start: March 1, 2010
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 10, 2025

Record last verified: 2025-02

Locations

US (1)