4‐Methylpyrazole: A Controlled Study of Safety in Healthy Human Subjects after Single, Ascending Doses

4‐Methylpyrazole (4‐MP), an inhibitor of alcohol dehydrogenase, is a possible future drug for the treatment of methanol and ethylene glycol intoxications and the severe ethanol‐disulfiram reaction. Therefore a placebo‐controlled, double‐blind, single‐dose, randomized, sequential, ascending‐dose “Phase I study” was performed in healthy volunteers in order to determine the tolerance of 4‐MP at dose levels of 10 (n= 4), 20 (n= 4), 50 (n= 4), and 100 mg/kg (n= 3). Along with each dose group, there were two placebos except with the 100 mg/kg group where there was only one placebo. In the 10 and 20 mg/kg group there were no side‐effects in any subject. At the 50 mg/kg level, three out of four subjects experienced slight to moderate nausea and dizziness from 0 to 2.5 h after dosing. In the 100 mg/kg group all three subjects reported side‐effects like nausea, dizziness, and vertigo, that were short‐lived in two subjects, but lasted up to 30 h in one subject The study was stopped after evaluation of the latter subject, so fewer subjects were completed in this last group. Despite these subjective side‐effects, there were no significant changes in objective clinical parameters like pulse, blood pressure, body temperature, or blood and urine chemistries. We conclude that at a single dose of 4‐MP (10–20 mg/kg) producing plasma levels within a probable therapeutic range, no side‐effects were attributed to 4‐MP.