title: 4-Methylpyrazole (4-MP) is effectively removed by haemodialysis in the pig model.
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.
authors.affiliation: Department of Medicine, Ullevaal Hospital, University of Oslo, Norway.
authors.forename: D
authors.initials: D
authors.lastname: Jacobsen
authors.forename: J
authors.initials: J
authors.lastname: Ostensen
authors.forename: L
authors.initials: L
authors.lastname: Bredesen
authors.forename: E
authors.initials: E
authors.lastname: Ullstein
authors.forename: K
authors.initials: K
authors.lastname: McMartin
mesh_terms: D000818:Animals; D005260:Female; D000077604:Fomepizole; D008297:Male; D011720:Pyrazoles / Q000097:blood* / Q000302:isolation & purification; D006435:Renal Dialysis; D013552:Swine
chemical_list: D011720:Pyrazoles; D000077604:Fomepizole