Theoretical changes in drug distribution resulting from changes in binding to plasma proteins and to tissues

Abstract

Abstract Concentrations of chlorpromazine fluctuate in the plasma of dogs and man after intravenous doses. The possibility that the fluctuations could arise from movement of the drug between tissue and plasma stores is examined theoretically. Calculations show that small changes in protein binding of drugs in plasma and tissues could cause redistribution of highly bound drugs between tissues and plasma. Redistribution would be greatest after changes in tissue binding of highly bound drugs. Fluctuations in chlorpromazine concentrations could be caused in this way.