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Excerpt
4-methyl pyrazole (4MP), a competitive inhibitor of alcohol deshydrogenase, is used to prevent production of toxic metabolites after poisoning by ethylene glycol. Its action appears as effective as ethanol with less side effects. The aim of our study is to develop and validate a simple method to measure 4MP in plasma, and to determine its pharmacokinetics in a patient intoxicated by methanol. A gas chromatographic method has been developed with a splitless capillary injector and a nitrogen phosphorus detector. The injector and detector T° were 280 and 350°C respectively. The carrier gas was helium. The extraction was obtained by addition of K2CO3, propylphenazone (PP) as internal standard, and ethyl acetate to 300μL of plasma sample. 2μL of the upper organic layer were injected into the system. Retention times of 4MP and PP were 3.98 and 9.56 min. The analytical validation of the method displayed a limit of detection of 1.4μg/mL, a linear analytical range of 5-50μg/mL, and coefficient of variations < 6.34%. This method has been used for monitoring a patient admitted for methanol poisoning (0.5 g/L methanol and 0.9g/L formic acid on admission). The 48h 4MP treatment consisted of a loading oral dose of 15mg/kg followed by lower maintenance doses. The treatment was well tolerated and resulted to plasma 4MP concentrations ranging from 10-20μg/mL, close to the target therapeutic concentration of 15 μg/mL. Bioavailability was excellent, apparent elimination t 1/2 and Vd of 4MP were evaluated 19.8h, and 0.65L/kg respectively. The patient made a complete recovery.
