title: Pharmacokinetics 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.
authors.affiliation: Division of Biomedicine, National Defence Research Establishment, Umeå, Sweden.
authors.forename: A G
authors.initials: AG
authors.lastname: Nyberg
authors.forename: G
authors.initials: G
authors.lastname: Cassel
authors.forename: T
authors.initials: T
authors.lastname: Jeneskog
authors.forename: L
authors.initials: L
authors.lastname: Karlsson
authors.forename: R
authors.initials: R
authors.lastname: Larsson
authors.forename: M
authors.initials: M
authors.lastname: Lundström
authors.forename: L
authors.initials: L
authors.lastname: Palmer
authors.forename: S A
authors.initials: SA
authors.lastname: Persson
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000931:Antidotes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001285:Atropine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007277:Injections, Jet / Q000295:instrumentation*; D008297:Male; D010091:Oximes / Q000097:blood; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D013552:Swine
chemical_list: D000889:Anti-Arrhythmia Agents; D000931:Antidotes; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D001285:Atropine; D000110:Acetylcholinesterase; C022870:asoxime chloride