Pharmacokinetics of obidoxime in patients poisoned with organophosphorus compounds

Objectives- Reactivation of inhibited acetylcholinesterase (AChE) with oximes is a causal therapy of intoxication with organophosphorus compounds (OPs). Maximal oxime effects are expected when effective doses are administered as soon as possible and as long as reactivation can be anticipated. An obidoxime plasma level in the range of 10-20 mu M was estimated as appropriate. The achievement of this target was assessed in 34 severely OP-poisoned patients Methods After admission to the intensive care unit (ICU) the obidoxime regimen (250 mg i.v. as bolus, followed by 750 mg/24 h) was started and maintained as long as reactivation was possible. Plasma concentrations of obidoxime were determined by HPLC. Results. A total amount of 2269 +/- 1726 mg obidoxime was Infused over 65 h +/- 55 h resulting in a steady state plasma concentration of 14 5 +/- 7 3 mu M. Obidoxime was eliminated with t(1/2(1)) 2.2 and t(1/2(2)) 14 h. The volumes of distribution amounted to 0.32 +/- 0 1 L/kg (V((1))) and 0.28 +/- 0.12 (V((2))) L/kg. Postmortem examination of tissue in one patient showed obidoxime accumulation in cartilage, kidney and liver and pointed to brain concentrations similar to plasma concentration. Conclusions. Using the suggested obidoxime regimen, the targeted plasma concentration could be achieved. Obidoxime was eliminated biphasically and was well tolerated This result allows the recommendation of using this definite regimen for adults also in case of mass casualties. (C) 2010 Elsevier Ireland Ltd. All rights reserved.