Role of variability in explaining ethanol pharmacokinetics: research and forensic applications.

摘要: Variability in the rate and extent of absorption, distribution elimination ethanol has important ramifications clinical legal medicine. The speed absorption from gut depends on time day, drinking pattern, dosage form, concentration beverage, particularly fed or fasting state individual. During phase, a gradient exists between stomach, portal vein peripheral venous circulation. First-pass metabolism bioavailability are difficult to assess because dose-, time- flow-dependent kinetics. Ethanol is transported by bloodstream all parts body. equilibration governed ratio blood flow tissue mass. Arterial concentrations differ as function after drinking. low solubility lipids does not bind plasma proteins, so volume closely related amount water body, contributing sex- age-related differences disposition. bulk ingested (95-98%) metabolised remainder excreted breath, urine sweat. rate-limiting step oxidation conversion into acetaldehyde cytosolic alcohol dehydrogenase (ADH), which Michaelis-Menten constant (Km) 0.05-0.1 g/L. Moreover, this enzyme displays polymorphism, accounts for racial ethnic variations pharmacokinetics. When moderate dose ingested, zero-order operates large part blood-concentration course, since ADH quickly becomes saturated. Another ethanol-metabolising enzyme, cytochrome P450 2E1, higher Km (0.5-0.8 g/L) also inducible, that clearance increased heavy drinkers. Study design influences variability Oral intravenous administration, fasted state, might require different pharmacokinetic models. Recent work supports need multicompartment models describe disposition instead traditional one-compartment model with elimination. appropriate statistical analysis needed isolate between- within-subject components variation. Samples at improve estimation parameters reduce variability. pharmacokinetics stems combination both genetic environmental factors, nonlinear nature disposition, experimental design, subject selection strategy dependency. More document real-world situations.