4-Methylpyrazole (4-MP) is effectively removed by haemodialysis in the pig model
Jacobsen, D.; Østensen, J.; Bredesen, L.; Ullstein, E.; McMartin, K.; Jacobsen, D., Department of Medicine, Ullevaal Hospital, University of Oslo; Østensen, J., Institute for Experimental Research, Ullevaal Hospital, University of Oslo, Norway; Bredesen, L., Institute for Experimental Research, Ullevaal Hospital, University of Oslo, Norway; Ullstein, E., Department of Medicine, Ullevaal Hospital, University of Oslo; McMartin, K., Department of Pharmacology, Louisiana State University Medical Center, Shreveport, Louisiana, USA
Журнал:
Human and Experimental Toxicology
Дата:
1996
Аннотация:
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 m<sup>2</sup> 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.
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