Invasion and distribution of methanol

Abstract

After the enzyme systems responsible for methanol oxidation were blocked by ethanol, five test persons were given methanol at a dose of approximately 10 mg/kg weight, once orally and once parenterally. Taking into account the endogenous blood methanol levels detectable before the administration of methanol, C0 concentrations of 11.1-15.9 mg/kg were reached. This corresponds to a distribution volume of approximately 0.77 +/- 0.07 l/kg, which is comparable to the 0.78 +/- 0.09 l/kg obtained for ethanol. After parenterally administering methanol as a bolus, the distribution half-life was on average 8 min (range: 3.8-13.8 min). After oral administration of methanol diluted in 100 ml water on an empty stomach, invasion took place with a half-life of approximately 5 min (3.8-6.9 min). In one case, however, due to vegetative disturbances the invasion half-life was 23.1 min.

Recommendations for the Role of Extracorporeal Treatments in the Management of Acute Methanol Poisoning

“…Methanol is metabolized by ADH to formaldehyde, which is rapidly oxidized to formic acid, which spontaneously dissociates to formate and a hydrogen ion Formate is the principle mediator of morbidity and mortality from methanol poisoning Elimination Other routes of methanol elimination include renal (clearance, 5-6 mL/min) and nonrenal (presumed respiratory; 7-13 mL/min) (19,46) Methanol undergoes either first-or zero-order elimination depending on the dose (15)(16)(17)(18)(19) The apparent elimination half-life of methanol is 2.3-13.7 hr in the absence of antidote therapy (9,71) The inhibition of ADH-mediated metabolism of methanol prolongs its apparent elimination half-life to a mean of 54 hr (9-11) although it may vary between 9 and 87 hr (9-11, 17, 30, 37-39, 78-82) ADH = alcohol dehydrogenase.…”

“…15, persistent metabolic acidosis despite adequate supportive measures and antidotes, serum anion gap higher than 24 mmol/L; or, serum methanol concentration 1) greater than 700 mg/L (21.8 mmol/L) in the context of fomepizole therapy, 2) greater than 600 mg/L or 18.7 mmol/L in the context of ethanol treatment, 3) greater than 500 mg/L or 15.6 mmol/L in the absence of an alcohol dehydrogenase blocker; in the absence of a methanol concentration, the osmolal/ osmolar gap may be informative; or, in the context of impaired kidney function. Treatment includes the administration of antidotes (ethanol or fomepizole and folic/folinic acid) and consideration of extracorporeal treatment for correction of acidemia and/or enhanced elimination.…”

Medical toxicology and public health—Update on research and activities at the centers for disease control and prevention, and the agency for toxic substances and disease registry

“…One study examining human experimental exposure to methanol found that the inhalational absorption half-life was 0.8 hours when volunteers were exposed to methanol vapors at TLV of 200 ppm for 4 hours [14]. Once absorbed, methanol appears to be rapidly and fairly well distributed, with a volume of distribution of 0.7 l/kg, consistent with its hydrophilicity [17][18][19]. Methanol has also been reported to cross the placenta and result in neonatal toxicity [20].…”

Handbook of Drug Interactions

“…Coadministration of multiple doses of cimetidine has been found to diminish the elimination of a number ofbenzodiazepines (Table 20), that include: adinazolam (156), alprazolam (157,158), bromazepam (159), chlordiazepoxide (160), clobazam (161), clorazepate (162), diazepam (149,(163)(164)(165)(166)(167)(168), flurazepam (169), midazolam (140,170), nitrazepam (171), nordiazepam (172), and triazolam (157,158,173). Single doses of cimetidine seem to have milder effect, but have been found to diminsih the elimination of diazepam (174) and midazolam (154,1 75,176) in a dose-dependent fashion (Table 20).…”

“…The improved clinical response is, however, in direct contrast with the effect of carbamazepine on TCA metabolism. Therapeutic druglevel reviews and clinical studies have shown that patients also treated with carbamazepine have amounts of parent and demethylated TCA in blood reduced by as much as 60%, in comparison with patients treated with a comparable dose ofTCA alone (145,(159)(160)(161). These effects by carbamazepine on TCA metabolism appear to be mediated through induction ofCYPIA2 and CYP3A4 enzymes (106,162).…”