Inhalation pharmacokinetics of 1,2-dichloroethane after different dietary pretreatments of male Sprague-Dawley rats

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Abstract
The effect of the pretreatment of male Sprague-Dawley rats with phenobarbital (PB), butylated hydroxyanisole (BHA) and disulfiram (DSF) on the inhalation kinetics of 1,2-dichloroethane [ethylene dichloride (EDC)] was studied by the gas uptake method. A closed recirculating system was constructed and characterized. The rate curves in all the pretreatment regimens showed saturable dependence on EDC concentration. These saturable dependencies (Michalis-Menten) appeared to be associated with enzymatic metabolism. In general, a two-compartment, steady-state pharmacokinetic model described the uptake data. Data were transformed by Hanes plots to calculate the inhalational Km, the ambient EDC concentration at which uptake proceeded at half maximum rate, and Vmax, the maximum rate of uptake (i. e., maximum rate of metabolism). Although PB and BHA pretreatments did not affect the Km of EDC, PB pretreatment increased the Vmax while DSF pretreatment decreased both the Km and Vmax.