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4-Methylpyrazole (4-MP) is effectively removed by haemodialysis in the pig model

Department of Medicine, Ullevaal Hospital, University of Oslo

J. Østensen

Institute for Experimental Research, Ullevaal Hospital, University of Oslo, Norway

L. Bredesen

Institute for Experimental Research, Ullevaal Hospital, University of Oslo, Norway

E. Ullstein

Department of Medicine, Ullevaal Hospital, University of Oslo

K. McMartin

Department of Pharmacology, Louisiana State University Medical Center, Shreveport, Louisiana, USA

The safety and pharmacokinetics of the alcohol dehydro genase inhibitor 4-MP have recently been evaluated and its clinical use in ethylene glycol poisoning in France is promising. The dialysability of 4-MP is not known. This is important as hemodialysis is one of the cornerstones in the treatment of (late) ethylene glycol and methanol poison ings. We therefore studied the dialysability of 4-MP in the pig model. Anesthesized pigs (maintained on respirator) given 4-MP, 10 mg/kg, served as controls (n=3) to the pigs (n=3) given 15 mg/kg and hemodialyzed for 4 h. 4-MP plasma elimination curves for both groups were compared for 12 h and dialysance data calculated. 4-MP (MW 82) was removed by the same rate as urea (MW 60) by the 0.3 m² dialysator, thus indicating no significant protein binding of 4-MP. The mean dialysance of 4-MP (and urea) in the three pigs were 61 (63), 51 (53) and 56 (48) ml/min, at a blood flow of 75 ml/min. The amount of 4-MP removed by hemodialysis in 4 h was 57-76 mg compared to a urinary excretion of 1-3 mg over 12 h. We conclude that the dialysablity of 4-MP is significant and this must be taken into account when these two treatment procedures are combined.

Key Words: 4-methylpyrazole • methanol • ethylene glycol • poison ing

Human & Experimental Toxicology, Vol. 15, No. 6, 494-496 (1996)
DOI: 10.1177/096032719601500606


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