Am. J. Respir. Crit. Care Med., Vol 151, No. 5, 05 1995, 1331-1335.
Effect of a novel potent platelet-activating factor antagonist, modipafant, in clinical asthma
LM Kuitert, RM Angus, NC Barnes, PJ Barnes, MF Bone, KF Chung, AJ Fairfax, TW Higenbotham, BJ O'Connor and B Piotrowska
Department of Thoracic Medicine, London Chest Hospital and National Heart and Lung Institute, United Kingdom.
Platelet-activating factor (PAF), proposed as an important inflammatory
mediator in asthma, reproduces several of the features of asthma, such as
microvascular leakage, mucus secretion, bronchoconstriction, and possibly
increased airway responsiveness. Modipafant (UK-80,067) is the
(+)-enantiomer of UK-74,505, a potent and specific PAF antagonist. We have
assessed the effect of modipafant over 28 d in adult subjects with
moderately severe asthma in a placebo-controlled parallel group study. A
total of 218 patients with asthma were enrolled into the single-blind
run-in, of whom 120 (93 males and 27 females, mean age 41.0 yr) entered the
double-blind treatment phase after demonstrating symptomatic asthma in the
final week of the single-blind run-in phase. Patients could take up to 1600
micrograms inhaled corticosteroid and an inhaled beta 2 agonist as rescue
medication. A total of 59 patients with asthma took modipafant (one 50 mg
capsule twice daily), and 61 took matched placebo. There was no significant
difference between placebo and modipafant in diurnal variation in PEF,
morning and evening PEF, clinic FEV1, rescue bronchodilator usage, symptom
score, or airway responsiveness. We previously showed that the racemate
UK-74,505 had no effect on antigen challenge, and this study shows that the
active (+)- enantiomer modipafant has no effect in chronic asthma. This
suggests that PAF is not an important mediator in asthma.
