Pharmacokinetics and pharmacodynamics of thiazinamium in asthmatic patients

Eur J Clin Pharmacol. 1987;33(3):237-42. doi: 10.1007/BF00637555.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Asthma / physiopathology
  • Forced Expiratory Volume
  • Heart Rate / drug effects
  • Humans
  • Injections, Intramuscular
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Promethazine / administration & dosage
  • Promethazine / analogs & derivatives*
  • Promethazine / pharmacokinetics*
  • Promethazine / therapeutic use

Substances

  • Promethazine