Prediction of in vivo kinetic constants for metabolism of inhaled vapors from kinetic constants measured in vitro.

Benzene and toluene are metabolized by microsomal preparations in a closed metabolism flask. The Km values for benzene and toluene were 8.0 and 10.3 microM; the Vmax values were 17.2 and 20.8 nmol/g liver/min, respectively. By the use of a toxicokinetic model which acknowledges the potential for perfusion limitations on in vivo metabolism, the in vivo Km values (in terms of atmospheric concentration) for benzene and toluene were calculated based on the constants determined in vitro. The predicted in vivo constants were 0.20 and 0.21 mg/L, respectively. In vivo Km values experimentally determined by gas uptake techniques in the same strain of animal were 0.13 and 0.59 mg/L for benzene and toluene, respectively. For benzene predicted values and observed values for Km gave good correlation. The values for toluene did not correlate quite as well. The Vmax values predicted by direct conversion of the values obtained in vitro were 3.3 and 4.7 mg/kg/hr for benzene and toluene, respectively, and agreed well with the respective values observed in vivo of 2.2 and 4.6 mg/kg/hr. The model appeared capable of accurately predicting in vivo Km values from in vitro constants. Vmax values were predicted directly from in vitro constants.