Pharmacological assessment of the duration of action of glycopyrrolate vs tiotropium and ipratropium in guinea‐pig and human airways

1 Our study was aimed at investigating the duration of the bronchodilator action of the antimuscarinc drug glycopyrrolate compared to tiotropium and ipratropium. 2 In the guinea‐pig isolated trachea, the time ( t 1/2 ) necessary for a contractile response to carbachol (0.3  μ M ) to return to 50% recovery after washout of the antagonist was studied. The offset of the antagonist effect of glycopyrrolate, tiotropium and ipratropium (10 n M each) was t 1/2 =4.0±0.5, >4.5 and 0.5±0.1 h, respectively. At 4.5 h from the washout of the antagonist, the recovery of the response to carbachol was 50±8, 10±4 and 70±7%, respectively. 3 In the human isolated bronchus, the offset of the bronchodilator effects of glycopyrrolate (3 n M ), tiotropium (1 n M ) and ipratropium (10 n M ) was t 1/2 =3.7±0.2; >6 and 3.0±0.2 h, respectively. At 6.0 h from the washout of the antagonist, the recovery of the response to carbachol (1  μ M ) was 101±10, 27±3 and 110±10%, respectively. 4 In anaesthetized guinea‐pigs, acetylcholine‐induced bronchoconstriction was markedly reduced by intratracheal instillation of glycopyrrolate (3 nmol kg −1 ; 88.1±4% inhibition), tiotropium (1.3 nmol kg −1 ; 86.2±5% inhibition) or ipratropium (1.45 nmol kg −1 ; 88.1±10% inhibition). These inhibitory effects assessed 3 or 24 h after antagonist administration were reduced to 69.9±5 and 29.7±6%; 28.3±5 and 14.2±5% for glycopyrrolate and ipratropium, respectively, whereas they remained stable (83.5±4; 70.6±6) for tiotropium. The residual inhibitory effect of glycopyrrolate was also assessed at 16 h from administration, and proved to be as low as that found at 24 h (31.2±10 vs 29.7±6%, respectively). 5 In conclusion, glycopyrrolate‐induced bronchodilation has a longer duration than that of ipratropium, but less than that of tiotropium. The efficacy of a possible glycopyrrolate‐based therapy for asthma or chronic obstructive pulmonary disease given once‐a‐day is not guaranteed by the present investigation.British Journal of Pharmacology (2006) 148 , 291–298. doi: 10.1038/sj.bjp.0706724