Evaluation of the systemic anticholinergic activity of nasally administered ipratropium bromide.
Plasma concentrations of nasally inhaled ipratropium bromide were analyzed in eight healthy volunteers by using a sensitive radioreceptor assay (RRA). The rate of saliva secretion, heart rate and changes in visual accommodation were quantitated in order to measure possible systemic anticholinergic drug effects. 240 micrograms of ipratropium bromide (40 micrograms each nostril, repeated twice at 15 min intervals) were inhaled nasally in a double blind, randomized, placebo-controlled experiment. Ipratropium bromide absorbed fast, and peak plasma concentrations of the drug (257 +/- 55 pg/ml) were detected as soon as 5 min after the last inhalation (at 35 min from the beginning). The plasma levels of ipratropium bromide decreased rapidly, being only 86 +/- 7 pg/ml one hour after the last inhalation. These low concentrations of ipratropium bromide indicate that only a small portion of it absorbs after nasal application, which is consistent with the lack of any systemic anticholinergic drug effects in our subjects. It is concluded that nasally applied ipratropium bromide is not likely to cause systemic anticholinergic side-effects, even in doses exceeding the therapeutic recommendations.
Laurikainen
E
E
Dept. of Otorhinolaryngology, Turku University Hospital, Finland.
Koulu
M
M
Kaila
T
T
Scheinin
M
M
Isalo
E
E
D000042:Absorption; D000281:Administration, Intranasal; D000328:Adult; D001286:Atropine Derivatives / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D009241:Ipratropium / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D010276:Parasympatholytics; D011869:Radioligand Assay; D011897:Random Allocation; D012463:Saliva / Q000378:metabolism
D001286:Atropine Derivatives; D010276:Parasympatholytics; D009241:Ipratropium