Pharmcokinetics of HI‐6 and atropine in anaesthetized pigs after administration by a new autoinjector

Abstract

A newly developed autoinjector (Astra Tech, Sweden) containing 500 mg HI-6 and 2 mg atropine sulphate was tested in anaesthetized normal pigs. The pharmacokinetics and pharmacodynamics of the drugs after administration by the autoinjector were compared with those after conventional needle and syringe delivery intramuscularly and intravenously. Cardiopulmonary parameters were monitored and serum concentrations of oxime, atropine, and acetylcholinesterase were determined in blood samples taken at intervals over a 6 h period postinjection. After injection in anaesthetized pigs, both HI-6 and atropine were absorbed rapidly and completely from the injection site. Therapeutic serum concentrations of HI-6, arbitrarily taken as 4 micrograms mL-1, were reached within 1 min of intravenous and autoinjector administration, and within 5 min of intramuscular injection. The concentrations remained above this level for 3-4 h. There were no significant changes in acetylcholinesterase activity, mean arterial blood pressure, or respiration frequency after injection of HI-6 and atropine sulphate. The heart rates increased significantly after administration of the two drugs (cardioacceleration defined as > or = 5% increase in heart rate), regardless of the technique employed. Our results show that HI-6 and atropine sulphate can be given intramuscularly by the new autoinjector with the same effectiveness and speed as when given intravenously. Irrespective of the injection technique, no overt signs of toxicity were observed at the drug concentrations used.

Dramatic Increase in Cerebral Blood Flow following Soman Intoxication If Signs of Symptoms Can Be Seen

“…They concluded that loss of central respiratory drive is the predominant cause of nerve agent-induced respiratory failure. We have demonstrated earlier that the respiratory failure during Soman intoxication can be reversed by antidotal treatment with HI 6 and atropine without reactivation of blood AChE activity 8 Advances in Toxicology [32]. These results indicate that a noncholinergic mechanism is involved in the respiratory effect of Soman.…”

Development and validation of a sensitive HPLC method for the quantification of HI-6 in guinea pig plasma and evaluated in domestic swine

“…Previous methods have been used to determine HI-6 plasma concentrations in mice [11], guinea pigs [17], rats [5,6,9], rabbits [10], canines [8,9], swine [7,16,18], non-human primates [17][18][19] and man [4].…”

“…To identify and quantify HI-6 in plasma samples, a rapid high performance liquid chromatography (HPLC) method was required. HPLC techniques for the quantitative analysis of HI-6 have been reported that generally require relatively tedious extractions [4], lengthy chromatographic separations [4][5][6][7] and large sample volumes [5]. The method reported here was designed to improve on previous methods and also be in compliance with Good Laboratory Practices, so as to enable the data to be used for regulatory submission.…”

Haematological and Biochemical Changes in Response to Stress Induced by the Administration of Amikacin Injection by Autoinjector in Animals

“…Since the human dose is close to the LD 50 of rat the full dose of 500 mg and the partial dose of 300 mg (2 doses) could not be tolerated by the rats. But, a drug like atropine sulphate was tolerated by pigs when the human dose was administered by autoinjectors 14 . In the experimental dose (63 mg/mL cartridge) none of the haematological and biochemical parameters showed any significant difference compared with the control, manual injection and through autoinjector when administered to rat intraperitoneally, showing that the delivery of amikacin through the autoinjector was well tolerated by the rats.…”