Pharmacokinetics of fungal (1-3)-beta-D-glucans following intravenous administration in rats.
Glucans are microbial cell wall carbohydrates that are shed into the circulation of patients with infections. Glucans are immunomodulatory and have structures that are influenced by bacterial or fungal species and growth conditions. We developed a method to covalently label carbohydrates with a fluorophore on the reducing terminus, and used the method to study the pharmacokinetics following intravenous administration of three highly purified and characterized glucans (glucan phosphate, laminarin and scleroglucan) that varied according to molecular size, branching frequency and solution conformation. Elimination half-life was longer (3.8+/-0.8 vs. 2.6+/-0.2 and 3.1+/-0.6 h) and volume of distribution lower (350+/-88 ml/kg vs. 540+/-146 and 612+/-154 ml/kg) for glucan phosphate than for laminarin and scleroglucan. Clearance was lower for glucan phosphate (42+/-6 ml/kg h) than for laminarin (103+/-17 ml/kg h) and scleroglucan (117+/-19 ml/kg h). Since plasma levels at steady state are inversely related to clearance, these differences suggest that pharmacokinetics could favor higher blood levels of glucans with certain physicochemical properties.
Rice
Peter J
PJ
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA. rice@etsu.edu
Lockhart
Brent E
BE
Barker
Luke A
LA
Adams
Elizabeth L
EL
Ensley
Harry E
HE
Williams
David L
DL
D000818:Animals; D019540:Area Under Curve; D005936:Glucans / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006207:Half-Life; D007275:Injections, Intravenous; D008033:Limulus Test; D016014:Linear Models; D008297:Male; D011134:Polysaccharides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D047071:beta-Glucans / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
D005936:Glucans; D011134:Polysaccharides; D047071:beta-Glucans; C480175:glucan phosphate; C045938:scleroglucan; C008247:laminaran; C033363:beta-1,3-glucan