Tolerability and pharmacokinetics of L-648,051. A leukotriene D4-receptor antagonist, in healthy volunteers

Détails

ID Serval
serval:BIB_B10FF920C18A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Tolerability and pharmacokinetics of L-648,051. A leukotriene D4-receptor antagonist, in healthy volunteers
Périodique
European Journal of Clinical Pharmacology
Auteur(s)
Biollaz  J., Stahl  E., Hsieh  J. Y., Distlerath  L., Jaeger  A., Leuenberger  P., Schelling  J. L.
ISSN
0031-6970 (Print)
Statut éditorial
Publié
Date de publication
1988
Volume
33
Numéro
6
Pages
603-7
Notes
Clinical Trial
Controlled Clinical Trial
Journal Article
Résumé
Two formulations of L-648,051 (L) were studied [intravenous (i.v.) and aerosol (A)] in two separate trials. Study I (i.v.) involved 4 normal male subjects in a single blind dose ranging study where good systemic tolerability and safety was shown. However, dose dependent local irritation at the injection site was observed at all dose levels (35, 52.5 and 70 mg/5 min infusion). L has a high systemic clearance rate (1.2 1/min), a small volume of distribution (4.41) and a short plasma half-life (2.4 min). Study II (A) involved 16 normal male volunteers who received incremental aerosolized doses of L from 0.1 to 1.6 mg in a double-blind, placebo controlled, dose ranging study. Complaints of mild local irritation or discomfort in the upper respiratory tract were the only significant findings. No dose relationship of these complaints could be shown. In conclusion, L is a safe and well tolerated drug when administered by aerosol. It causes dose related local, but not systemic, adverse experiences when administered i.v. In view of this tolerability and of its demonstrated activity against LTD4-challenge in animals, clinical efficacy studies with the aerosol formulation are warranted.
Mots-clé
Adult Dose-Response Relationship, Drug Drug Tolerance Humans Injections, Intravenous *Keto Acids Male Phenylbutyrates/administration & dosage/*pharmacokinetics Receptors, Leukotriene Receptors, Prostaglandin/*drug effects SRS-A/*metabolism *Sulfones
Pubmed
Web of science
Création de la notice
25/01/2008 11:40
Dernière modification de la notice
03/03/2018 20:35
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