TRIMEDOXIME AND HI-6 - KINETIC COMPARISON AFTER INTRAVENOUS ADMINISTRATION TO MICE

The intravenous pharmacokinetics of the oximes HI-6 idinium-1-(((4-car bamoil-pyridinio)metoxy)methyl)- 2-(hydroxyiminomethyl)dichloride mono hydrate), (132.54 mu mol/kg) and edoxime(1,1'-(1,3'-propanedyl)bis((4- hydroxyimino) methyl)-pyridinium dibromide), (55.98 mu mol/kg) in mice was investigated. The concentrations of oximes in plasma determined b y high pressure liquid chromatography (HPLC) corresponded to a two-com partment pharmacokinetic open model. The oximes were rapidly eliminate d from mice plasma, with half-times of 57.93 min. for HI-6 and 108.08 min. for trimedoxime. Although the oximes passed from circulation into the tissues at approximately the same rate, their transport back to t he central compartment was two-times slower in the case of trimedoxime : t(1/2k21) was 77.9 min. for trimedoxime and 41.7 min. for HI-6. The total body clearance (CItot) of HI-6 was about 25% higher than that of trimedoxime. The central compartment volume of HI-6 distribution (V-1 ) was greater, whereas the volume of distribution of the peripheral co mpartment (V-2) was lower for about 35% with respect to the correspond ing parameters of trimedoxime. The calculated pharmacokinetic paramete rs for the oxime HI-6 and trimedoxime show that trimedoxime is elimina ted more slowly in mice, and penetrates better into the peripheral com parment where it remains longer.