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The leukotriene-receptor antagonist MK-0679 blocks airway obstruction induced by inhaled lysine-aspirin in aspirin-sensitive asthmatics.
Eur Respir J. 1993 Jul; 6(7):1018-26.ER

Abstract

Drugs which block the action or formation of the cysteinyl leukotrienes (LTC4, LTD4 and LTE4) inhibit asthmatic responses evoked by allergen, exercise and cold dry air. The purpose of this study was to determine whether the specific leukotriene-receptor antagonist MK-0679 could block the airway obstruction induced by aspirin (acetylsalicylic acid (ASA)) in aspirin-intolerant asthmatics. Eight asthmatics (mean age 45 yrs), with an average history of asthma and ASA-sensitivity of about 10 yrs duration, were subjected to bronchial provocation with lysine-ASA. Baseline ASA-sensitivity was first determined in an open prestudy session by inhalation of cumulative doses of lysine-ASA to establish the dose of ASA decreasing forced expiratory volume in one second (FEV1) by 20% (PD20). Rechallenge with lysine-ASA was performed on two different occasions, 1 h after oral administration of placebo, or 750 mg of MK-0679, under double-blind conditions, in a randomized, cross-over design. Leukotriene formation was estimated by the measurement of urinary LTE4. The lysine-ASA challenge was highly reproducible (geometric mean for group PD20 being identical for the open prestudy and the placebo session), and was associated with a post-challenge increase in urinary LTE4. In contrast, after MK-0679, there was a rightward shift in the dose response relationship for all eight subjects (median shift being 4.4 fold), with three of the subjects failing to produce a 20% decrease in FEV1 despite inhalation of the highest dose of lysine-ASA feasible to deliver.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Dept of Thoracic Medicine, Karolinska Hospital, Stockholm, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8396534

Citation

Dahlén, B, et al. "The Leukotriene-receptor Antagonist MK-0679 Blocks Airway Obstruction Induced By Inhaled Lysine-aspirin in Aspirin-sensitive Asthmatics." The European Respiratory Journal, vol. 6, no. 7, 1993, pp. 1018-26.
Dahlén B, Kumlin M, Margolskee DJ, et al. The leukotriene-receptor antagonist MK-0679 blocks airway obstruction induced by inhaled lysine-aspirin in aspirin-sensitive asthmatics. Eur Respir J. 1993;6(7):1018-26.
Dahlén, B., Kumlin, M., Margolskee, D. J., Larsson, C., Blomqvist, H., Williams, V. C., Zetterström, O., & Dahlén, S. E. (1993). The leukotriene-receptor antagonist MK-0679 blocks airway obstruction induced by inhaled lysine-aspirin in aspirin-sensitive asthmatics. The European Respiratory Journal, 6(7), 1018-26.
Dahlén B, et al. The Leukotriene-receptor Antagonist MK-0679 Blocks Airway Obstruction Induced By Inhaled Lysine-aspirin in Aspirin-sensitive Asthmatics. Eur Respir J. 1993;6(7):1018-26. PubMed PMID: 8396534.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The leukotriene-receptor antagonist MK-0679 blocks airway obstruction induced by inhaled lysine-aspirin in aspirin-sensitive asthmatics. AU - Dahlén,B, AU - Kumlin,M, AU - Margolskee,D J, AU - Larsson,C, AU - Blomqvist,H, AU - Williams,V C, AU - Zetterström,O, AU - Dahlén,S E, PY - 1993/7/1/pubmed PY - 1993/7/1/medline PY - 1993/7/1/entrez SP - 1018 EP - 26 JF - The European respiratory journal JO - Eur Respir J VL - 6 IS - 7 N2 - Drugs which block the action or formation of the cysteinyl leukotrienes (LTC4, LTD4 and LTE4) inhibit asthmatic responses evoked by allergen, exercise and cold dry air. The purpose of this study was to determine whether the specific leukotriene-receptor antagonist MK-0679 could block the airway obstruction induced by aspirin (acetylsalicylic acid (ASA)) in aspirin-intolerant asthmatics. Eight asthmatics (mean age 45 yrs), with an average history of asthma and ASA-sensitivity of about 10 yrs duration, were subjected to bronchial provocation with lysine-ASA. Baseline ASA-sensitivity was first determined in an open prestudy session by inhalation of cumulative doses of lysine-ASA to establish the dose of ASA decreasing forced expiratory volume in one second (FEV1) by 20% (PD20). Rechallenge with lysine-ASA was performed on two different occasions, 1 h after oral administration of placebo, or 750 mg of MK-0679, under double-blind conditions, in a randomized, cross-over design. Leukotriene formation was estimated by the measurement of urinary LTE4. The lysine-ASA challenge was highly reproducible (geometric mean for group PD20 being identical for the open prestudy and the placebo session), and was associated with a post-challenge increase in urinary LTE4. In contrast, after MK-0679, there was a rightward shift in the dose response relationship for all eight subjects (median shift being 4.4 fold), with three of the subjects failing to produce a 20% decrease in FEV1 despite inhalation of the highest dose of lysine-ASA feasible to deliver.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0903-1936 UR - https://www.unboundmedicine.com/medline/citation/8396534/The_leukotriene_receptor_antagonist_MK_0679_blocks_airway_obstruction_induced_by_inhaled_lysine_aspirin_in_aspirin_sensitive_asthmatics_ L2 - https://medlineplus.gov/asthma.html DB - PRIME DP - Unbound Medicine ER -