title: Review of the basic and clinical pharmacology of sulfobutylether-beta-cyclodextrin (SBECD).
abstract: 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-beta-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.
authors.affiliation: Pfizer, Inc., New York, New York, USA. luked@pfizer.com
authors.forename: David R
authors.initials: DR
authors.lastname: Luke
authors.forename: Konrad
authors.initials: K
authors.lastname: Tomaszewski
authors.forename: Bharat
authors.initials: B
authors.lastname: Damle
authors.forename: Haran T
authors.initials: HT
authors.lastname: Schlamm
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D004285:Dogs; D005079:Excipients / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D011743:Pyrimidines / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D014230:Triazoles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D065819:Voriconazole; D047392:beta-Cyclodextrins / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D000935:Antifungal Agents; D005079:Excipients; D011743:Pyrimidines; D014230:Triazoles; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D065819:Voriconazole