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Reply to Letter to the Editor “Free Drug Fraction Versus Free Drug Concentration”

J Clin Psychiatry 2000;61(6):449 [letter]

Letter to the Editor

Sir: We thank Dr. Pies for his thoughtful comments and agree that the free, non–protein-bound concentration of drugs in plasma is more closely correlated with drug effect than total concentration. In addition, for many drugs and situations, including drug-drug interactions that result in displacement of drugs from plasma protein binding sites, the increase in free drug concentration is transient. An exception to this generalization would be a drug with a high hepatic intrinsic clearance whose plasma protein binding is nonrestrictive for elimination and that is administered intravenously.