The effect of oral terfenadine alone and in combination with flurbiprofen on the bronchoconstrictor response to inhaled adenosine 5'-monophosphate in nonatopic asthma.
Inhaled adenosine and adenosine 5'-monophosphate (AMP) cause bronchoconstriction in atopic and nonatopic asthmatics by a mechanism believed to involve histamine release from airway mast cells and an interaction with neural reflexes. In the present study, we have investigated the effect of oral terfenadine 180 mg, flurbiprofen 100 mg, and the drug combination on AMP-induced bronchoconstriction in eight nonatopic asthmatic subjects with a mean age of 53.8 +/- 5.6 yr. The provocation concentrations of histamine and AMP required to produce a 20% decrease in FEV1 (PC20) were determined to be 2.5 (range, 0.2 to 16.3) and 50.1 (range, 1.5 to 841) mg/ml, respectively, representing a potency difference of 17.8-fold on a molar basis. In subsequent time-course studies, the bronchoconstrictor response to inhalation of the PC20 histamine was suppressed completely by terfenadine and the drug combination, but unaffected by flurbiprofen. Terfenadine alone and flurbiprofen alone inhibited bronchoconstriction provoked by the PC20 AMP by 49.8 +/- 5.5% (p less than 0.01) and 31.9 +/- 7.9% (p less than 0.01), respectively, when areas under the FEV1 time curves were compared with placebo, the difference between the two treatments not being significant (p = 0.06). The drug combination inhibited the response to AMP by 60.0 +/- 8.3% (p less than 0.01), this being significantly greater than with flurbiprofen (p less than 0.01), but not with terfenadine alone. These data implicate both histamine and cyclooxygenase products in the bronchoconstrictor response to AMP.
Phillips
G D
GD
Southampton General Hospital, United Kingdom.
Holgate
S T
ST
D000249:Adenosine Monophosphate / Q000008:administration & dosage; D000280:Administration, Inhalation; D000284:Administration, Oral; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000379:methods; D003251:Constriction, Pathologic / Q000139:chemically induced / Q000188:drug therapy; D004341:Drug Evaluation; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage*; D005541:Forced Expiratory Volume; D006632:Histamine / Q000008:administration & dosage; D006634:Histamine H1 Antagonists / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011422:Propionates / Q000008:administration & dosage*; D016593:Terfenadine
D001559:Benzhydryl Compounds; D006634:Histamine H1 Antagonists; D011422:Propionates; D000249:Adenosine Monophosphate; D005480:Flurbiprofen; D016593:Terfenadine; D006632:Histamine