pharmacokinetic studies on oximes in organophosphate poisoning: a mini review

Organophosphate (OP) poisoning is one of the most common causes of poisoning in developing countries especially in Southeastern Asia. Poisoning with phosphorus-containing organic chemicals or OP compounds can be managed with antidotes like oximes which are potential reactivators of acetylcholinesterase (AChE). The efficacy of oxime therapy in OP poisoned patients mainly depends upon various factors such as different dose plans, infusion rate of oximes, genetic differences of patients, type of oxime used and chemical nature of the OP compound ingested. Studies on pralidoxime kinetics in OP poisoned patients have shown that reactivation of AChE depends on the plasma concentration of oximes as well as OP compounds. The plasma concentration of oximes mainly depends on the dose plan from intermittent injection to continuous infusion after a loading dose. The incontrovertible fact is that the intermittent dosing of oximes results in deep troughs in blood pralidoxime/oxime levels (BPL) whereas continuous infusion of oximes maintains steady state plasma concentrations. Many published literature also highlighted pralidoxime via continuous infusion results in better outcomes with minimum fluctuation in BPL compared to intermittent dosing. At therapeutic doses, adverse effects of oximes are reported to be minimal. But high BPL is associated with some common adverse effects including dizziness, blurred vision and diastolic hypertension. Considering all the facts, it is important to note that kinetic studies of oximes are useful not only in deciding the dose regimen, but also in predicting the possible side-effects.