Nonliner tissue disposition: salicylic acid in rat brain

A model was developed to detect nonlinear disposition of a drug in a tissue. The model was experimentally tested relating to salicylic acid disposition in the brain. Experimental data obtained in rats are reported for doses of 25 and 40 mg/kg ip. The parameters measured for each dose were the ratio of the area under the brain concentration-time curve to the area under the plasma concentration-time curve and the ratio of the maximum brain concentration of salicylic acid to the plasma concentration at that point in time. The ratios increased with dose; furthermore, ratios calculated using plasma concentrations corrected for plasma protein binding were dose dependent. Calculations performed on literature data for salicylic acid disposition in mouse brain corroborated the results of this sutdy. The existence of a saturable transport system for the elimination of salicylic acid from the brain is supported by the data presented. The rationale necessary to apply the model to any tissue is discussed.