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[Pharmacokinetics and pharmacodynamics of nikethamide after endotracheal administration in dogs].

Five dogs were anaesthetized by using i.v. 30 mg.kg-1 Na-pentobarbiturate. For each dog, the tracheostomy was done and a sterized rubber tube was inserted into the tracheal tract. Through the rubber tube, 10 ml sterized nikethamide (Nik) solution was rapidly injected into the tract via 10 ml syringe and 5 forceful ventilations were performed immediately with the aid of a balloon in 30 s. Following tracheal administration (ET) of Nik 8.3 or 25 mg.kg-1 in dogs the pharmacokinetics and pharmacodynamics were studied. Blood Nik concentrations were determined by phosphorimetric method. It was shown that the absorption of Nik via tracheal tract was very quick. The blood Nik levels were 7.9 and 10.6 micrograms.ml-1 at 0.5 min and reached the maxima of 12.8 and 31.9 micrograms.ml-1, at 2.5 min, respectively, which was higher than that of i.v. Nik 8.3 mg.kg-1. Time course of Nik concentrations in plasma after ET 8.3 and 25 mg.kg-1 were fitted to a 2-compartment open model with T1/2Ka 0.48 and 0.85 min, T1/2 alpha 2.37 and 1.68 min, T 1/2 beta 114 and 130 min, AUC 1201 and 2790 micrograms.min.ml-1, bioavailability 84.7% and 65.5%, respectively. One minute after i.v. or ET Nik (8.3 or 25 mg.kg-1), respiration rate and tidal volume were increased and reached the maxima after 5 min. The recovery of respiration rate and tidal volume were proportional to the blood Nik concentration after 5-45 min with a linear regression coefficient of 0.9. The results indicated that ET Nik may be used instead of i.v. in resuscitation.