Ethanol
Ethanol. Two-step hepatic metabolism: alcohol dehydrogenase (ADH) → acetaldehyde → aldehyde dehydrogenase (ALDH) → acetate. ADH is saturable with Km ≈ 80 mg/L…
Two-step hepatic metabolism: alcohol dehydrogenase (ADH) → acetaldehyde → aldehyde dehydrogenase (ALDH) → acetate. ADH is saturable with Km ≈ 80 mg/L peripheral blood (≈ 0.008% BAC), so above ~100 mg/L elimination becomes near-zero-order at Vmax ≈ 230 mg/L/h (≈ 15-20 mg/dL/hr in BAC). CYP2E1 is the inducible high-Cp second pathway, prominent in chronic drinkers. Pharmacologically a positive allosteric modulator of GABA-A and NMDA antagonist at intoxicating concentrations.
PK: MY MODEL-CLASS PRIOR IS REFUTED — THIS RECORD IS RIGHT, AND SAYING SO MATTERS. I expected a first-order half-life on a drug that follows zero-order kinetics. There is no half-life stored at all: elimination runs on the solver Michaelis-Menten parameters, and BOTH CONSTANTS VERIFY VERBATIM — "This would be equivalent to a blood ethanol disappearance rate of 230 mg/L/h if metabolism took place at its maximum rate" and "The elimination rate is half of the elimination capacity at a peripheral blood ethanol concentration (Km) of about 80 mg/L" — as does the volume. THE REFERENCE ALREADY IN THIS RECORD IS DOING REAL WORK: an independent intravenous-infusion cohort gives "The average Vm[0.232 mg/(ml x hr)] and Km[0.0821 mg/ml]", corroborating both to within 0.9% and 2.6% FROM A DIFFERENT ROUTE AND A DIFFERENT STUDY, and the internal check closes too. A CAVEAT IS RECORDED THAT IS NOT A DEFECT: every parameter here is WHOLE-BLOOD referenced, so the curve this record emits is a blood alcohol concentration rather than a plasma one, about 1.15 times lower — the set is internally consistent and NO SINGLE VALUE SHOULD BE "CORRECTED" INTO PLASMA UNITS. The one weak field is the absorption rate, which appears nowhere in the citation and which that paper explicitly declines to commit to, saying "Little attention has been paid to evaluation of potential models" of absorption. The bioavailability is one minus a stated extraction ratio, which is definitional but describes a quantity the same abstract calls flow- and rate-dependent.
Pharmacokinetics
- Oral — F 80% · Vd 37 L
Sources: PMID:3319346, PMID:1261158