Accumulation of the solvent vehicle sulphobutylether beta cyclodextrin sodium in critically ill patients treated with intravenous voriconazole under renal replacement therapy

In four patients suffering from renal insufficiency and intermittent dialysis therapy who needed a treatment with intravenous voriconazole as a reserve antifungal at the intensive care unit of the Mainz University Hospital the trough levels of voriconazole and sulphobutylether beta cyclodextrin sodium were measured.A 75-year-old woman showed a maximal sulphobutylether beta cyclodextrin sodium plasma level of 145 μg/ml in the initial phase. After a few days renal function recovered and the plasma levels came down to less than 20 μg/ml. In contrast to this patient with a recovery of renal function the remaining three patients showed renal failure during the complete period of intravenous treatment with voriconazole. In these patients an accumulation of sulphobutylether beta cyclodextrin sodium plasma levels was determined with a maximum of 523 μg/ml in a 18-year-old man, 409 μg/ml in a 57-year-old man, and 581 μg/ml in a 47-year-old man.The present data indicate an accumulation of sulphobutylether beta cyclodextrin sodium in patients treated with intravenous voriconazole and dialysis therapy. Fortunately, no toxic effects were observed, although the accumulated dose values were lower but comparable with those used in previous toxicity studies with animals.The triazole antifungal, voriconazole, was introduced for the treatment of life-threatening fungal infections. The drug, which is available for both oral and intravenous administration, has broad-spectrum activity against pathogenic yeasts, dimorphic fungi and opportunistic moulds [1,2]. As voriconazole has limited aqueous solubility, the intravenous form includes the solvent vehicle sulphobutylether beta cyclodextrin sodium as a novel delivery system [3]. In healthy subjects sulphobutylether beta cyclodextrin sodium is rapidly eliminated with a terminal half-life of 1.6 hours. The clearance of sulphobutylether beta cyclodextrin sodium is linearly related to creatinine clearance and accumulation has been described in