Literature DB >> 8793532

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

D Jacobsen1, J Ostensen, L Bredesen, E Ullstein, K McMartin.   

Abstract

The safety and pharmacokinetics of the alcohol dehydrogenase 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 poisonings. 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 dialysability of 4-MP is significant and this must be taken into account when these two treatment procedures are combined.

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Year:  1996        PMID: 8793532     DOI: 10.1177/096032719601500606

Source DB:  PubMed          Journal:  Hum Exp Toxicol        ISSN: 0960-3271            Impact factor:   2.903


  2 in total

1.  4-methylpyrazole monitoring during haemodialysis of ethylene glycol intoxicated patients.

Authors:  H Faessel; P Houze; F J Baud; J M Scherrmann
Journal:  Eur J Clin Pharmacol       Date:  1995       Impact factor: 2.953

Review 2.  Antidotes for poisoning by alcohols that form toxic metabolites.

Authors:  Kenneth McMartin; Dag Jacobsen; Knut Erik Hovda
Journal:  Br J Clin Pharmacol       Date:  2016-01-04       Impact factor: 4.335

  2 in total

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