PHARMACOKINETICS OF THE ACETYLCHOLINESTERASE OXIME REACTIVATOR, HI-6, IN RHESUS-MONKEYS (MACACA-MULATTA) - EFFECT OF ATROPINE, DIAZEPAM, AND METHOXYFLURANE ANESTHESIA

The pharmacokinetics of the bispyridinium oxime HI‐6 (CAS reg. no. 34433–31–3;l‐(((4‐aminocarbonyl)pyridinio)methoxyl)methyI)‐2‐((hydroxyimino)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‐6 were 27 min, 8–6 ml min−1 kg−1 and 0.34 I 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. Copyright © 1990 John Wiley & Sons, Ltd.