Inhalation pharmacokinetics based on gas uptake studies

Abstract

Inhalation pharmacokinetics of acetone in rats was studied using gas uptake techniques. Under conditions of negligible metabolism (saturation of metabolizing enzymes) the coefficient of distribution K _eq between organism and gas phase was 220 which confirmed that acetone is mainly (but not exclusively) distributed within the body water compartment. The metabolic elimination of acetone from the animals followed strict Michaelis-Menten saturation kinetics; the K _m corresponded to 160 ppm in the atmosphere, v _max was 230 μmol · h⁻¹ · kg⁻¹. A shift in the distribution pattern of acetone under conditions of prevalent metabolism was theoretically predicted and experimentally proven; as the partial process of metabolic elimination was dose-dependent, this “depleted” the animal compartment from acetone in a dose-dependent fashion causing a shift in the “steady-state-constant”, K _st .

Part of the acetone which was metabolically eliminated (4.7%) appeared in the urine as formate within 7 days after ending a 48-h exposure to acetone; this excretion was linear with time. The data suggested existence of a formate pool in the organism from which formate was released with delay. Hence, limitations may be inferred as to the applicability of urinary formate excretion as a quantitative indicator for changing conditions of acetone exposure.