Impact of chlorpromazine self-association on its apparent binding constants with cyclodextrins: Effect of SBE7-β-CD on the disposition of chlorpromazine in the rat
✍ Scribed by Michelle P. McIntosh; Nathania Leong; Kasiram Katneni; Julia Morizzi; David M. Shackleford; Richard J. Prankerd
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 192 KB
- Volume
- 99
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
Chlorpromazine is an antipsychotic agent with poor aqueous solubility. Complexation with SBE 7 -b-CD can aid intravenous delivery through increasing the apparent solubility of chlorpromazine. However, chlorpromazine has also been known to self-associate. This selfassociation 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 SBE 7 -b-CD containing formulation. Pharmacokinetic studies of chlorpromazine in the presence and absence of SBE 7 -b-CD were undertaken in rats. The binding constant of SBE 7 -b-CD and chlorpromazine was studied relative to chlorpromazine concentration via fluorescence. The selfassociation of chlorpromazine was studied by fluorescence and UV-visible spectrophotometry. Urinary excretion of intact chlorpromazine increased in the presence of SBE 7 -b-CD. The SBE 7b-CD binding constant of chlorpromazine is highly concentration dependent and the variation can be attributed to the self-association of chlorpromazine. 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. ß 2010 Wiley-