Transporter Mediated Uptake of Montelukast

NCT00513760 | Completed

• 2 other identifiers: 3271132-03215-003
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Leukotriene receptor antagonists (LTRAs) are frequently prescribed to reduce the symptoms associated with asthma. Singulair, 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 turnstiles to allow drugs to move from the intestine to the bloodstream and are known to be inhibited by components of citrus juice. The activity of a transporter can be influenced by individual genetic variability. We think that Singulair requires help from a transport protein to be absorbed and that genetic variability in this transporter leads to variability in the blood level of Singulair. In this proposal we will use citrus juice (grapefruit and orange) to inhibit intestinal membrane transport proteins and show that Singulair requires these transporters to be efficiently absorbed. 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; Drug Interactions

Outcome Measures

Primary Outcomes (1)

• Area under the concentration vs. time curve for the serum concentration of montelukast when coingested with grapefruit juice, orange juice, or Gatorade.

  Within 12 hours after administration of a single 10 mg dose.

Secondary Outcomes (1)

• Improvement in respiratory function as assessed by spirometry, and impulse oscillometry vs. serum concentration of montelukast.

  Within 12 hours after administration of a single 10 mg dose.

Study Arms (3)

1

EXPERIMENTAL

Coingestion of 240 ml of grapefruit juice with 10 mg of montelukast.

Dietary Supplement: Grapefruit juice

2

ACTIVE COMPARATOR

Coingestion of 240 ml of orange juice with 10 mg of montelukast.

Dietary Supplement: Orange Juice

3

PLACEBO COMPARATOR

Coingestion of 240 ml of Gatorade with 10 mg of montelukast.

Dietary Supplement: Gatorade

Interventions

Grapefruit juice DIETARY_SUPPLEMENT

Coingestion of 240 ml of grapefruit juice with 10 mg of montelukast.

Also known as: Brand: Great Value frozen concentrated grapefruit juice(Walmart).

1

Orange Juice DIETARY_SUPPLEMENT

Coingestion of 240 ml of orange juice with 10 mg of montelukast.

Also known as: Brand: Winn Dixie orange juice (Winn Dixie).

2

Gatorade DIETARY_SUPPLEMENT

Coingestion of 240 ml of Gatorade with 10 mg of montelukast.

Also known as: Brand: Gatorade Rain.

3

Eligibility Criteria

• Age: 15 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Doctor diagnosed asthma.
• Must not be taking any medications except for inhaled steroids.

You may not qualify if:

• Clinical conditions other than asthma.
• Upper respiratory tract infection within the past 30 days.
• Gastrointestinal conditions.
• Unable to stop taking or are required to begin taking any type of oral medication for the duration of the trial

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)

• Lima JJ. Treatment heterogeneity in asthma: genetics of response to leukotriene modifiers. Mol Diagn Ther. 2007;11(2):97-104. doi: 10.1007/BF03256228.

  PMID: 17397245 BACKGROUND

• Lima JJ, Zhang S, Grant A, Shao L, Tantisira KG, Allayee H, Wang J, Sylvester J, Holbrook J, Wise R, Weiss ST, Barnes K. Influence of leukotriene pathway polymorphisms on response to montelukast in asthma. Am J Respir Crit Care Med. 2006 Feb 15;173(4):379-85. doi: 10.1164/rccm.200509-1412OC. Epub 2005 Nov 17.

  PMID: 16293801 BACKGROUND

Related Links

• Merck's Singulair site

MeSH Terms

Conditions

Asthma

Interventions

gatorade

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: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Reserach Scientist

Study Record Dates

• First Submitted: August 7, 2007
• First Posted: August 9, 2007
• Study Start: June 1, 2007
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 10, 2025

Record last verified: 2025-02

Locations

US (1)