title: Pharmacokinetics of the acetylcholinesterase oxime reactivator, HI-6, in rhesus monkeys (Macaca mulatta): effect of atropine, diazepam, and methoxyflurane anesthesia.
abstract: The pharmacokinetics of the bispyridinium oxime HI-6 (CAS reg. no. 34433-31-3; 1-(((4-aminocarbonyl)pyridinio)methoxy)methyl)-2-[hydroxy i mino)methyl)- pyridinium dichloride) was investigated in rhesus monkeys (Macaca mulatta). The effects of methoxyflurane anesthesia, administration of atropine with and without diazepam were determined on the serum half-life (t1/2), clearance rate (CL), and the volume of distribution (Vd) following intramuscular (IM) administration of HI-6 (30 mg kg-1). The control t1/2, CL and Vd of HI-offere 27 min, 8.6 ml min-1 kg-1 and 0.34 l kg-1, respectively. These parameters were unaffected by the co-administration of either atropine (0.5 mg kg-1, IM) or atropine and diazepam (0.5 mg kg-1, IM + 0.2 mg kg-1 IV, respectively). Methoxyflurane anesthesia resulted in a significant increase in the HI-6 t1/2 to 61 min concomitant with a decrease in the CL to 4.1 ml min-1 kg-1 with no change in the Vd. The increase in the t1/2 of HI-6 in methoxyflurane anesthetized monkeys is probably the result of a decrease in the clearance rate and, thus, excretion of HI-6 by the kidneys.
authors.affiliation: Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alta, Canada.
authors.forename: J G
authors.initials: JG
authors.lastname: Clement
authors.forename: M J
authors.initials: MJ
authors.lastname: Lee
authors.forename: K J
authors.initials: KJ
authors.lastname: Simons
authors.forename: C J
authors.initials: CJ
authors.lastname: Briggs
mesh_terms: D000758:Anesthesia; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D006207:Half-Life; D008253:Macaca mulatta; D008297:Male; D008733:Methoxyflurane; D010091:Oximes; D011726:Pyridinium Compounds / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D008733:Methoxyflurane; D001285:Atropine; C022870:asoxime chloride; D003975:Diazepam