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Pharmacokinetics of the acetylcholinesterase oxime reactivator, HI‐6, in rhesus monkeys ( Macaca mulatta ): Effect of atropine, diazepam, and methoxyflurane anesthesia
Author(s) -
Clement John G.,
Lee Mary J.,
Simons Keith J.,
Briggs Colin J.
Publication year - 1990
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510110307
Subject(s) - methoxyflurane , atropine , chemistry , diazepam , pharmacokinetics , volume of distribution , anesthetic , oxime , pharmacology , anesthesia , halothane , medicine , biochemistry , organic chemistry
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 ( t 1/2 ), clearance rate (CL), and the volume of distribution ( V d ) following intramuscular (IM) administration of HI‐6 (30 mg kg −1 ). The control t 1/2 , CL and V d 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 t 1/2 to 61 min concomitant with a decrease in the CL to 4.1 ml min −1 kg −1 with no change in the V d . The increase in the t 1/2 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.