School of Pharmacy, University of Otago, Dunedin, New Zealand.
Clin Pharmacokinet. 2011 Apr;50(4):245-51. doi: 10.2165/11584250-000000000-00000.
Methanol is a toxic alcohol that can cause significant morbidity and mortality in overdose, while ethanol is a readily available and effective antidote. Little is known about the pharmacokinetics of methanol in the presence of ethanol and vice versa. This paper explores the influence of methanol and ethanol on the pharmacokinetics of each other along with the effect of continuous venovenous haemodiafiltration (CVVHD) on alcohol removal.
Multiple plasma, urine and dialysate samples were collected from a 42-year-old male who ingested 166 g of methanol. Methanol and ethanol concentrations in both plasma and urine were assayed and the concentration-time data were modelled using nonlinear mixed-effects modelling software NONMEM® VI. Simulations were performed using the final model parameters in MATLAB® software where a variety of initial doses and ethanol infusions were assessed.
The final model included a competitive metabolic interaction between methanol and ethanol as well as first-order elimination due to renal, CVVHD and an additional non-renal non-CVVHD mechanism. Simulations from the model show a loading dose of 28.4 g/70 kg of ethanol results in a target plasma concentration of 1 g/L. Due to the competitive interaction between methanol and ethanol, higher amounts of methanol require lower maintenance doses of ethanol but for longer. CVVHD was shown to increase the dose rate of ethanol required but to decrease the duration of the maintenance phase.
A detailed understanding of the pharmacokinetics of methanol and ethanol in the presence of each other is required to accurately determine the doses of ethanol required to treat different methanol poisonings.
甲醇是一种有毒的醇类物质，过量摄入会导致严重的发病率和死亡率，而乙醇是一种易得且有效的解毒剂。关于甲醇和乙醇在彼此存在的情况下的药代动力学以及连续静脉-静脉血液透析滤过（CVVHD）对酒精清除的影响，我们知之甚少。本文探讨了甲醇和乙醇对彼此药代动力学的影响，以及 CVVHD 对酒精清除的影响。
从一名摄入 166g 甲醇的 42 岁男性中采集了多个血浆、尿液和透析液样本。测定了血浆和尿液中甲醇和乙醇的浓度，并使用 NONMEM® VI 非线性混合效应建模软件对浓度-时间数据进行建模。使用 MATLAB®软件中的最终模型参数进行模拟，评估了各种初始剂量和乙醇输注。
最终模型包括甲醇和乙醇之间的竞争性代谢相互作用，以及由于肾、CVVHD 和另外一种非肾非 CVVHD 机制导致的一级消除。模型模拟显示，28.4g/70kg 的乙醇负荷剂量可使目标血浆浓度达到 1g/L。由于甲醇和乙醇之间的竞争性相互作用，较高剂量的甲醇需要较低的维持剂量，但维持时间较长。CVVHD 显示增加了所需乙醇剂量率，但减少了维持阶段的持续时间。
需要深入了解甲醇和乙醇在彼此存在的情况下的药代动力学，以准确确定治疗不同甲醇中毒所需的乙醇剂量。
