ISSN:
1432-1041
Keywords:
thiazinamium
;
asthma
;
pharmacokinetics
;
pharmacodynamics
;
optimal concentration
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary The pharmacokinetics and pharmacodynamics of thiazinamium (Multergan) were studied after intravenous and intramuscular administration to 7 males with chronic reversible airways obstruction. Disposition after i.v. administration was described by a clearance of 0.54 l·min−1, central compartment volume of 14.8 l, distribution rate constant 0.092 min−1, and an elimination rate constant of 0.0044 min−1. The corresponding estimates after i.m. administration were 0.324 l·min−1, 34.1 l, 0.035 min−1, and 0.0018 min−1. The bronchodilator response (expressed as % predicted FEV1) after i.v. administration was characterized by maximum increase in FEV1 of 33.9%, with an EC50 of 12.8 ng·ml−1 and an equilibration half-time of 11 min. Corresponding parameter estimates after i.m. administration were 32.2%, 18.8 ng·ml−1, and 9 min. Anticholinergic activity, measured by the change in heart rate after i.v. administration, showed maximum increase of 76 beats·min−1, with an EC50 of 176 ng·ml−1 and an equilibration half-time of 1.3 min. After i.m. administration the corresponding values were 120 beats·min−1, 250 ng·ml−1, and 3 min. The optimal plasma concentration of thiazinamium was about 100 ng·ml−1, which should give a near maximal bronchodilator response (over 80% of predicted normal) and a heart rate of about 100 beats·min−1.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00637555
