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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1993-4-30
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pubmed:abstractText |
To elucidate the role of leukotrienes (LT) in allergic asthma in humans the effect of MK-886, an LT biosynthesis inhibitor, was evaluated on antigen-induced early (EAR) and late (LAR) asthmatic reactions and bronchial responsiveness to histamine. Eight atopic men participated in a two-part, double-blind, placebo-controlled, crossover trial. MK-886 was administered in two oral doses of 500 mg and 250 mg, 1 h before and 2 h after allergen inhalation, respectively. Biochemical effects of MK-886 were evaluated by the inhibition of urinary LTE4 excretion and calcium ionophore-stimulated LTB4 biosynthesis in whole blood ex vivo. MK-886 significantly inhibited the EAR by 58.4% (AUC0-3 h) and the LAR by 43.6% (AUC3-7 h) when compared with placebo (p < 0.01). There was no difference in PC20 histamine 30 h post allergen challenge between MK-886 and placebo (0.33 and 0.27 doubling doses, p > 0.1). MK-886 inhibited calcium ionophore-stimulated LTB4 production in whole blood (54.2 +/- 25.6%) for up to 6 h post allergen challenge. LTE4 excretion in urine was inhibited by 51.5% during the EAR by as much as 80% during the LAR. This indicates that LT play a role in allergen-induced asthmatic reactions in humans in vivo and that LT synthesis inhibitors such as MK-886 should be further explored for the treatment of asthma.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Allergens,
http://linkedlifedata.com/resource/pubmed/chemical/Histamine,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/L 663536,
http://linkedlifedata.com/resource/pubmed/chemical/Leukotriene Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Leukotriene E4,
http://linkedlifedata.com/resource/pubmed/chemical/SRS-A
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0003-0805
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
147
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
839-44
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:8385430-Administration, Oral,
pubmed-meshheading:8385430-Adult,
pubmed-meshheading:8385430-Allergens,
pubmed-meshheading:8385430-Asthma,
pubmed-meshheading:8385430-Bronchial Provocation Tests,
pubmed-meshheading:8385430-Double-Blind Method,
pubmed-meshheading:8385430-Drug Evaluation,
pubmed-meshheading:8385430-Histamine,
pubmed-meshheading:8385430-Humans,
pubmed-meshheading:8385430-Indoles,
pubmed-meshheading:8385430-Leukotriene Antagonists,
pubmed-meshheading:8385430-Leukotriene E4,
pubmed-meshheading:8385430-Male,
pubmed-meshheading:8385430-SRS-A
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pubmed:year |
1993
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pubmed:articleTitle |
Oral leukotriene inhibitor (MK-886) blocks allergen-induced airway responses.
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pubmed:affiliation |
Clinical Pharmacology Department, Merck Research Laboratories, Rahway, NJ 07065.
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Randomized Controlled Trial
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