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

Details

Serval ID
serval:BIB_3383696409A6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Tolerability and pharmacokinetics of L-648,051. A leukotriene D4-receptor antagonist, in healthy volunteers.
Journal
European Journal of Clinical Pharmacology
Author(s)
Biollaz J., Stahl E., Hsieh J.Y., Distlerath L., Jaeger A., Leuenberger P., Schelling J.L.
ISSN
0031-6970 (Print)
ISSN-L
0031-6970
Publication state
Published
Issued date
1988
Volume
33
Number
6
Pages
603-607
Language
english
Notes
Publication types: Clinical Trial ; Controlled Clinical Trial ; Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
Adult, Dose-Response Relationship, Drug, Drug Tolerance, Humans, Injections, Intravenous, Keto Acids, Male, Phenylbutyrates/administration & dosage, Phenylbutyrates/pharmacokinetics, Receptors, Leukotriene, Receptors, Prostaglandin/drug effects, SRS-A/metabolism, Sulfones
Pubmed
Create date
03/05/2013 9:30
Last modification date
24/02/2022 6:34
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