Rats^[2]
A 300 g rat is administered with 1 mL of a 0.1 M SBE-β-CD solution containing 5.64 mg of Compound 1, and assuming an extracellular volume of 90 mL, less than 0.1% of the complex would rapidly dissociate due to the initial effects of dilution. This calculation, combined with the changing blood to plasma ratio in the presence of SBE-β-CD, provides a reasonable explanation for the observed differences in the blood and plasma profiles of Compound 1 after intravenous administration in either the cyclodextrin or cyclodextrin-free formulations. After IV administration of the cyclodextrin formulation, Compound 1 would initially be prevented from distributing into erythrocytes thereby resulting in a whole blood to plasma ratio of less than one. Subsequently, clearance of SBE-β-CD from the circulation would lead to changes in the complexation equilibrium such that the unbound fraction of Compound 1 would increase, thereby reestablishing normal blood to plasma partitioning (i.e. in favour of whole blood) and clearance.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Fukuda M, et al.Influence of sulfobutyl ether beta-cyclodextrin (Captisol) on the dissolution properties of a poorly soluble drug from extrudates prepared by hot-melt extrusion.Int J Pharm. 2008 Feb 28;350(1-2):188-196  [Content Brief]

  [2]. Charman SA, et al. Alteration of the intravenous pharmacokinetics of a synthetic ozonide antimalarial in the presence of a modified cyclodextrin. J Pharm Sci. 2006 Feb;95(2):256-67  [Content Brief]