Review of the basic and clinical pharmacology of sulfobutylether-β-cyclodextrin (SBECD)

• Published in: Journal of pharmaceutical sciences Vol. 99; no. 8; pp. 3291 - 3301
• Main Authors: Luke, David R., Tomaszewski, Konrad, Damle, Bharat, Schlamm, Haran T.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.08.2010; Wiley; American Pharmaceutical Association
• Subjects: Animals; Antifungal Agents - administration & dosage; Antifungal Agents - chemistry; Antifungal Agents - therapeutic use; beta-Cyclodextrins - adverse effects; beta-Cyclodextrins - chemistry; beta-Cyclodextrins - pharmacokinetics; beta-Cyclodextrins - toxicity; Biological and medical sciences; cyclodextrins; Dogs; Excipients - adverse effects; Excipients - chemistry; Excipients - pharmacokinetics; Excipients - toxicity; formulations; General pharmacology; glomerular filtration; Humans; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; pharmacokinetics; Pharmacology. Drug treatments; Pyrimidines - administration & dosage; Pyrimidines - chemistry; Pyrimidines - therapeutic use; Rats; renal clearance; SBECD; solubility; toxicology; Triazoles - administration & dosage; Triazoles - chemistry; Triazoles - therapeutic use; Voriconazole; glomerular filtration; Filtration; Pharmaceutical technology; renal clearance; Oligosaccharide; Solubility; SBECD; Review; Clearance; cyclodextrins; Kidney; β-Cyclodextrin; Cyclodextrin; Toxicology; formulations; Formulation; Clinical pharmacology; Oside polymer; Inclusion compound; Pharmacokinetics; Physicochemical properties
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1002/jps.22109

Despite its use in commercially available drugs such as intravenous voriconazole, there is little known in the medical literature about the clinical pharmacology of the solubilizing agent, sulfobutylether‐β‐cyclodextrin (SBECD). This paper summarizes all known data on SBECD pharmacokinetics and safety. In animals, volume of distribution approximates extracellular water volume and clearance is determined by the glomerular filtration rate. SBECD does not have any apparent effects on cardiovascular or respiratory systems, nor on autonomic and somatic functions in animals. In 1‐ and 6‐month studies in rats and dogs, the most noteworthy findings were renal tubular vacuolation and foamy macrophages in the liver and lungs. Mild toxicity in the kidney and liver as a consequence of vacuolation occurred in rats at the maximum dose of 3000 mg/kg, which is approximately 50‐fold greater than the SBECD dose typically administered in man. Doses up to 1500 mg/kg produced no histopathological evidence of toxicity in dog kidneys. SBECD has also been studied in healthy volunteers and subjects with renal dysfunction. Whereas plasma SBECD levels accumulate in those with renal compromise, there were no deleterious effects on renal function. Nonetheless, serum creatinine levels should be monitored in subjects with renal compromise receiving multiple doses of SBECD. © 2010 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3291–3301, 2010