Research article

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

Marc A von Mach¹ , Jürgen Burhenne² and Ludwig S Weilemann¹

¹Division of Intensive Care Medicine and Clinical Toxicology, II. Medical Department, University of Mainz, Langenbeckstr. 1, 55131 Mainz, Germany

²Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany

author email corresponding author email

BMC Clinical Pharmacology 2006, 6:6doi:10.1186/1472-6904-6-6

Published:	18 September 2006

Abstract

Background

Voriconazole was introduced for the treatment of life-threatening fungal infections. The intravenous form includes the solvent vehicle sulphobutylether beta cyclodextrin sodium which shows an impaired clearance under intermittent dialysis therapy. This investigation aimed to determine first clinical data on sulphobutylether beta cyclodextrin sodium blood levels to verify the risk for accumulation.

Methods

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.

Results

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.

Conclusion

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.