[Pharmacokinetics and pharmacodynamics of nikethamide after endotracheal administration in dogs]. 1994

R H Huang, and D Zhou, and C Q He
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.

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.

UI MeSH Term Description Entries
D007442 Intubation, Intratracheal A procedure involving placement of a tube into the trachea through the mouth or nose in order to provide a patient with oxygen and anesthesia. Intubation, Endotracheal,Endotracheal Intubation,Endotracheal Intubations,Intratracheal Intubation,Intratracheal Intubations,Intubations, Endotracheal,Intubations, Intratracheal
D008297 Male Males
D009552 Nikethamide A central nervous system stimulant. It was formerly used in the treatment of barbiturate overdose but is now considered to be of no value for such purposes and may be dangerous. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1229) Corethamid,Diethylnicotinamid,Nizethamid,Coramin,Coramine,Cordiamine,Nicethamide,Nicotinic Diethylamide,Diethylamide, Nicotinic
D012119 Respiration The act of breathing with the LUNGS, consisting of INHALATION, or the taking into the lungs of the ambient air, and of EXHALATION, or the expelling of the modified air which contains more CARBON DIOXIDE than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration ( Breathing
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013990 Tidal Volume The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. Tidal Volumes,Volume, Tidal,Volumes, Tidal

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