Pharmacokinetics and Pharmacodynamics of Oximes in Unanesthetized Pigs

Behavioral, Pharmacokinetic, and Cardiovascular Evaluation of Candidate Oximes in African Green Monkeys

“…The pharmacokinetic estimates of the highest dose tested (116 mmol/kg, im) in the current study using African green monkeys are similar to those obtained for MMB-4 (100 mmol/kg, im) in swine, except that a much longer elimination half-life (158 minutes) was reported in swine. 17 The elimination half-life of 46.84 minutes for 58 mmol/kg MMB-4 2 Cl in this study is similar to the 50 minutes half-life reported in rabbits at 50 mmol/kg. 18 The highest dose (116 mmol/kg or 55.5 mg/kg) of MMB-4 DMS tested in this study had an elimination half-life of 60.85 minutes, similar to values reported in rhesus monkeys.…”

“…A slight apparent increase in heart rate over vehicle following MMB-4 administration of either salt was noted but failed to reach statistical significance. Slight to modest increases in heart rate have been reported in swine 17 and beagles 20 following MMB-4 2Cl or MMB-4 DMS, respectively.…”

A liquid chromatographic–mass spectrometric (LC–MS) method for the analysis of the bis-pyridinium oxime ICD-585 in plasma: Application in a guinea pig model

“…However, in 3 animals (ID #2 and #6 with GB and ID #8 with GF challenge), plasma concentrations were 22-24 g/ml (Table 4). Pharmacokinetic studies of similar bis-pyridinium oximes, MMB-4 and HI-6, have been carried out in swine (Stemler et al, 1991) [10] and sheep (Moore et al, 1988) [11]. Data from the MMB-4 studies in swine indicate that the mean maximal plasma concentration (C max , 78 g/ml) was achieved in an average of 9.1 min following im administration of 32.9 mg/kg.…”

“…The % error was calculated by ([calculated concentration − actual concentration]/actual concentration) × 100. The limit of detection (LOD) and lower limit of quantification (LLOQ) were determined by the relationship 3S 0 and 10S 0 , respectively [8,9]. The S 0 was calculated and derived from the y intercept of plots of standard deviations from calibration curves as a function of the 5 lowest ICD-585 concentrations, respectively [8].…”

Swine models in the design of more effective medical countermeasures against organophosphorus poisoning

“…Swine have been used in research on pre-treatments such as pyridostigmine (Modell, 1991) or physostigmine (Stemler et al, 1990), atropine alone (Hornchen et al, 1989), oximes alone (Stemler et al, 1991) or two of the drugs in combination (Göransson-Nyberg et al, 1995a,b), and anticonvulsants (Levy et al, 2004). It is clear that the pharmacokinetics of treatment drugs could be altered during poisoning, depending on the agent dose, and this has been demonstrated previously in OP-poisoned mice treated with the oxime -methoxy)-methyl]-2-[hydroxyiminomethyl]-pyridinium) (Clement et al, 1988).…”