Trimedoxime and HI-6: kinetic comparison after intravenous administration to mice.

Abstract

The intravenous pharmacokinetics of the oximes HI-6 (pyridinium-1-(((4-carbamoil-pyridinio)metoxy)methyl)2 -(hydroxyiminomethyl)dichloride monohydrate), (132.54 mu mol/kg) and trimedoxime (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 by high pressure liquid chromatography (HPLC) corresponded to a two-compartment pharmacokinetic open model. The oximes were rapidly eliminated 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 the 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 (CI(tot)) 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 compartment (V(2)) was lower for about 35% with respect to the corresponding parameters of trimedoxime. The calculated pharmacokinetic parameters for the oxime HI-6 and trimedoxime show that trimedoxime is eliminated more slowly in mice, and penetrates better into the peripheral compartment where it remains longer.