Impact of chlorpromazine self-association on its apparent binding constants with cyclodextrins: Effect of SBE7-beta-CD on the disposition of chlorpromazine in the rat

Michelle Paula McIntosh, Nathania Leong, Kasiram Katneni, Julia Morizzi, David M Shackleford, Richard John Prankerd

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10 Citations (Scopus)


Chlorpromazine is an antipsychotic agent with poor aqueous solubility. Complexation with SBE7-beta-CD can aid intravenous delivery through increasing the apparent solubility of chlorpromazine. However, chlorpromazine has also been known to self-associate. This self-association can influence its capacity to interact with other chemical species, such as cyclodextrins. This study aimed to characterise the self-association and cyclodextrin binding properties of chlorpromazine, and the effect on pharmacokinetic parameters in rats when dosed with a SBE7-Beta-CD containing formulation. Pharmacokinetic studies of chlorpromazine in the presence and absence of SBE7-beta-CD were undertaken in rats. The binding constant of SBE7-beta-CD and chlorpromazine was studied by fluorescence and UV-visible spectrophotometry. Urinary excretion of intact chlorpromazine is highly concentration dependent and the variation can be attributed to the self-association of chlorpromezine. The apparent binding constant of chlorpromazine is highest at pharmacologically relevant concentrations, providing an explanation for the significant increase in renal chlorpromazine excretion observed in rats.
Original languageEnglish
Pages (from-to)2999 - 3008
Number of pages10
JournalJournal of Pharmaceutical Sciences
Issue number7
Publication statusPublished - 2010

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