Pharmacokinetics of the acetylcholinesterase oxime reactivator, HI-6, in rhesus monkeys (Macaca mulatta): Effect of atropine, diazepam, and methoxyflurane anesthesia
✍ Scribed by John G. Clement; Mary J. Lee; Keith J. Simons; Colin J. Briggs
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 315 KB
- Volume
- 11
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
The pharmacokinetics of the bispyridinium oxime HI-6 (CAS reg. no. 34433-3 1-3; 1 -(((4-aminocarbonyl)pyridinio)methoxy)methyl)-2-((hydroxyimino)methyl)-pyridinium dichloride) was investigated in rhesus monkeys (Macaca muluttu). The effects of methoxyflurane anesthesia, administration of atropine with and without diazepam were determined on the serum half-life (tl/z>, clearance rate (CL), and the volume of distribution ( v d ) following intramuscular (IM) administration of HI-6 (30 mg kg-I).
The control tlR, CL and v , of HI-6 were 27 min, 8.6 ml min-' kg-I and 0.34 1 kg-I, respectively. These parameters were unaffected by the co-administration of either atropine (0.5 mg kg-', IM) or atropine and diazepam (0.5 mg kg-', IM+O.2 mg kg-I IV, respectively). Methoxyflurane anesthesia resulted in a significant increase in the HI-6 t,, to 61 min concomitant with a decrease in the CL to 4.1 ml min-' kg-' with no change in the v d . The increase in the tIlz of HI-6 in methoxflurane anesthetized monkeys is probably the result of a decrease in the clearance rate and, thus, excretion of HI-6 by the kidneys.