Kinetic profile in blood and brain of the cholinesterase reactivating oxime HI-6 after intravenous administration to the rat.

The kinetic profile of the oxime HI-6, a potent cholinesterase reactivator, after iv administration of 0.1325 mmol/kg (50 mg/kg) to rats is described. The blood concentrations measured over a period of 300 min can be described by a two-compartment open model. Excretion occurred only by the kidney. Approximately 60% was excreted in unmetabolized form. Brain tissue concentrations were significantly above the detection limit of the HPLC analysis procedure even when a correction was made for the amount of HI-6 present in brain blood. The concentration in brain tissue is built up according to a rapid equilibration mechanism. Disappearance of HI-6 from brain occurred slowly compared to the elimination of HI-6 from blood. These findings are discussed in the light of the existing knowledge on the kinetic behavior of polar solutes in the central nervous system. Whether the concentrations of HI-6 built up in the brain are relevant for the therapy of organophosphate intoxications cannot be determined from the experiments described.