The elimination kinetics of methanol and the influence of ethanol

Abstract

Four male subjects aged between 20 and 29 years were given intravenous injections of methanol at a dosage of 10 mg per kg body weight, once without prior administration of ethanol, and once after oral ingestion of 0.3 g ethanol per kg body weight. The serum methanol concentration was monitored over the next 5 h (after methanol administration alone) and 6-7 h (after methanol administration following ethanol ingestion). The elimination of methanol administered alone was found to follow first-order kinetics with a rate constant for the elimination phase of 0.475-0.259 h-1, corresponding to an elimination half-life of 1.8-3.0 h. When ethanol was also administered methanol oxidation was found to be completely blocked until the blood ethanol concentration had fallen to 0.2 g/kg. When the ethanol concentration had dropped to zero, methanol elimination followed exactly the same course as that observed in the experiment without prior administration of ethanol (k: 0.378-0.231 h-1; t1/2: 1.5-2.7 h).

Formate in serum and urine after controlled methanol exposure at the threshold limit value.

“…Because this study did not have a control group and the sample size was small, a definitive conclusion cannot be drawn. Yet the findings are consistent with methanol pharmacokinetic parameters such as half-life, volume of distribution, and elimination rate at low concentrations (18,21,24 …”

Treatment of acute methanol poisoning with fomepizole

“…In untreated overdose, methanol follows zero-order kinetics, about 8.5 mg/dl being eliminated each hour [25]. In subtoxic doses, methanol elimination apparently follows first-order kinetics, with a half-life in the range of 1.4±3.3 h [26]. Under ethanol monotherapy, methanol's half-life is about 43 h [27].…”

The Utility of an Alcohol Oxidase Reaction Test to Expedite the Detection of Toxic Alcohol Exposures

“…4,6 Following ingestion, the development of a high anion gap may be delayed for 8-24 hours, during which time the toxic metabolites accumulate. 3,7,8 The osmol gap and anion gap may or may not be present due the state of the metabolism of the toxic alcohols, the quantity ingested, and the delay prior to assessment. 3,9,10 The laboratory technique chosen to define osmolarity and the formula used for measuring osmolality for establishing the osmol gap are neither sensitive nor specific for these toxic alcohols.…”

“…[9][10][11][12][13][14] The earlier appropriate therapy is initiated for methanol or ethylene glycol ingestions, the better the outcome in preventing the serious consequences of blindness, renal dysfunction, neurotoxicity, acidemia, metabolic acidosis, pancreatitis, and death. [15][16][17] Therapies include altering the toxic alcohol's metabolism with antidotal treatment using ethanol, 8,15,18 fomepizole, 19,20 removal of the alcohols by hemodialysis, 13,18,21,22 supportive care with sodium bicarbonate, 13 and fluid resuscitation, 13 and the administration of adjuvant therapies (thiamine, pyridoxine, and leucovorin 2 ) appropriate to the toxin ingested.…”