Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center - Shreveport, Shreveport, LA, 71130-3932, USA.
School of Medicine, University of Colorado, Aurora, CO, USA.
J Med Toxicol. 2022 Jan;18(1):19-29. doi: 10.1007/s13181-021-00862-3. Epub 2021 Oct 25.
Fomepizole is an anti-metabolite therapy that is used to diminish the toxicity from methanol or ethylene glycol. Although its elimination kinetics have been well described in healthy human subjects, the elimination in poisoned patients have only been described in a few isolated cases. This study was designed to relate the elimination of fomepizole in a series of poisoned patients to that in healthy humans.
Plasma samples from 26 patients in the clinical trials of the use of fomepizole for methanol and ethylene glycol poisoning were analyzed for fomepizole concentrations. The elimination of fomepizole was assessed after individual doses, both during and without intermittent hemodialysis.
In methanol- and ethylene glycol-poisoned patients, fomepizole had a volume of distribution of 0.66-0.68 L/kg. After repeated doses of fomepizole, the minimum trough concentration averaged 86-109 µmol/L, which is 10 times higher than the minimum therapeutic concentration. In healthy human subjects, fomepizole elimination follows Michaelis-Menten kinetics and has been calculated as zero-order elimination rates. Zero-order elimination rates averaged 13 and 17 μmol/L/h in methanol and ethylene glycol patients, respectively, compared to 6-19 μmol/L/h in healthy subjects. Elimination during intermittent hemodialysis followed first-order kinetics, with a half-life of 3 h.
Plasma concentrations during the repeated dosing confirmed that the recommended dosing schedule, with and without intermittent hemodialysis, maintained therapeutic concentrations throughout the treatments. Fomepizole elimination in poisoned patients at therapeutic plasma concentrations appears be similar to that reported previously in healthy human subjects.
法莫替丁是一种抗代谢疗法，用于减少甲醇或乙二醇的毒性。尽管其在健康人体中的消除动力学已得到很好的描述，但中毒患者的消除情况仅在少数孤立病例中有所描述。本研究旨在将一系列中毒患者中法莫替丁的消除情况与健康人体中的消除情况进行比较。
对接受法莫替丁治疗甲醇和乙二醇中毒的 26 例临床试验患者的血浆样本进行法莫替丁浓度分析。在个体剂量后评估法莫替丁的消除情况，包括在间歇性血液透析期间和不进行间歇性血液透析时。
在甲醇和乙二醇中毒患者中，法莫替丁的分布容积为 0.66-0.68 L/kg。重复用法莫替丁后，最低谷浓度平均为 86-109 μmol/L，是最低治疗浓度的 10 倍。在健康人体中，法莫替丁的消除遵循米氏-门坦动力学，并已计算为零级消除率。甲醇和乙二醇患者的零级消除率平均分别为 13 和 17 μmol/L/h，而健康受试者分别为 6-19 μmol/L/h。间歇性血液透析期间的消除遵循一级动力学，半衰期为 3 小时。
重复给药期间的血浆浓度证实，推荐的给药方案，包括和不包括间歇性血液透析，在整个治疗过程中维持治疗浓度。在治疗性血浆浓度下，中毒患者中法莫替丁的消除情况似乎与以前在健康人体中报道的相似。
