Dear EditorI read with interest the report by Cober et al1 describing adverse events in dogs receiving intravenously administered amiodarone (Amiodarone IV) containing the cosolvents polysorbate 80 and benzyl alcohol. The events described are quite similar to those we encountered during recent toxicology studies2 designed to compare the currently marketed formulation utilized by Cober (containing the cosolvents polysorbate 80 and benzyl alcohol) with a recently approved formulationa that utilizes β-cyclodextrin to solubilize amiodarone rather than the cosolvents. After induction of anesthesia, dogs (n = 7 per group) received either PM101 or Amiodarone IV. The initial response of the dogs treated with Amiodarone IV included hypoactivity, swollen ears, paws, muzzle, and periorbital region, and hyperemia of the ear pinnae. These responses were severe enough to warrant discontinuing the infusion to allow the animals to recover. These clinical signs in the Amiodarone IV group dogs were attributed to histamine release induced by polysorbate 80, one of the vehicle components of Amiodarone IV.3 The dogs were treated with an antihistamine and corticosteroid, and the infusion was successfully resumed the next day after an additional dose of the antihistamine. In contrast, no unusual signs or clinical signs were seen during dosing with PM101. No other physical or histological changes were noted in either dosing group during the study. Development of PM101 is the most recent effort to provide a formulation of amiodarone for IV use without the cosolvents polysorbate 80 and benzyl alcohol. PM101 contains sulfobutylether-7-β-cyclodextrin (Captisolb) to enhance the water solubility of amiodarone. Cyclodextrins are present in over 30 marketed drug formulations. These cyclic oligosaccharides have a hydrophilic central core that forms a noncovalent complex with a lipophilic moiety of the drug, and the hydrophilic surface of the molecule maintains the aqueous solubility of the complex. In the case of PM101, sulfobutylether-7-β-cyclodextrin enhances the water solubility of amiodarone by 70-fold. In the stock solution, this cyclodextrin remains in equilibrium with amiodarone, but after IV infusion, the equilibrium favors immediate release of amiodarone into the blood. PM101 has been shown to be bioequivalent with Amiodarone IV in humans.4 Cushing5 also has shown that PM101 has minimal to no hemodynamic effects in dogs and provides additional evidence of the role of the cosolvents in producing adverse hemodynamic effects in this model. PM101 recently was approved for use in humans by the Food and Drug Administration and will be available in the United States in early 2010. aPM101, Nexterone, Prism Pharmaceuticals, King of Prussia, PA bCaptisol, CyDex Pharmaceuticals Inc, Lenexa, KS