Modeling of pharmacokinetic and pharmacodynamic behavior of nivalin in anaesthetized cats.
The pharmacokinetic behaviour of nivalin (galanthamine hydrobromide) and its effect on the contractile response of electrically stimulated m. tibialis anterior were simultaneously studied after an i.v. administered dose of 3 mg/kg in cats. The determination of some basic pharmacokinetic parameters revealed that nivalin was distributed in a large volume (Vss = 2.17L/kg) and was quickly eliminated (t0.5 of elimination was 1.7 h), the area under the plasma concentration-time curve (AUC was 5.93 micrograms . h/ml and the total clearance (CL) - 1.05 L/h . kg. The pharmacological effect appeared almost instantly after nivalin administration, went through a maximum and slowly decreased for a period of 1.5-2 hours. Linear and logarithmic-logistic functions were used to detect the correlation between the pharmacokinetic and the pharmacodynamic data. The calculated correlation coefficients showed that the linear function better described the relationship between plasma concentrations and tibial muscle contractile response than the logarithmic-logistic function. In comparison with the classical anticholinesterase drugs nivalin showed some advantages concerning its pharmacokinetics, namely the prolonged residence in the cat's body and, as a result, a longer-lasting pharmacological effect.
D000818:Animals; D002415:Cats; D005702:Galantamine / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects*
D005702:Galantamine