Pharmacokinetics and pharmacodynamics of nikethamide after endotracheal administration in dogs
Huang, R.H.; Zhou, D.; He, C.Q.
Zhongguo Yao Li Xue Bao 15(3): 271-274
1994
ISSN/ISBN: 0253-9756 PMID: 7976386 Document Number: 438682
Five dogs were anaesthetized by using iv 30 mg cntdot kg-1 Na-pentobarbiturate. For each dog, the tracheostomy was done and a sterilized rubber tube was inserted into the tracheal tract. Through the rubber tube, 10 ml sterilized 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 cntdot kg-1 in doges 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 mu-g cntdot ml-1 at 0.5 min and reached the maxima of 12.8 and 31.9 mu-g cntdot ml-1, at 2.5 min, respectively, which was higher than that of iv Nik 8.3 mg cntdot kg-1. Time course of Nik concentrations in plasma after ET 8.3 and 25 mg cntdot kg-1 were fitted to a 2-compartment open model with T-1/2Kalpha 0.48 and 0.85 min, T-1/2alpha 2.37 and 1.68 min, T-1/2beta 114 and 130 min, AUC 1201 and 2790 mu-g cntdot min cntdot min-, bioavailability 84.7% and 65.5%, respectively. One minute after iv or ET Nik (8.3 or 25 mg cntdot 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 iv in resusciatation.