Pharmacokinetics of fungal (1–3)-β- 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 fluo...

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Bibliographic Details
Published in:International immunopharmacology 2004-09, Vol.4 (9), p.1209-1215
Main Authors: Rice, Peter J, Lockhart, Brent E, Barker, Luke A, Adams, Elizabeth L, Ensley, Harry E, Williams, David L
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Area Under Curve
beta-Glucans - administration & dosage
beta-Glucans - chemistry
beta-Glucans - pharmacokinetics
Biological and medical sciences
Fungal
Glucans
Glucans - administration & dosage
Glucans - chemistry
Glucans - pharmacokinetics
Half-Life
Immunomodulation
Injections, Intravenous
Intravenous
Limulus Test
Linear Models
Male
Medical sciences
Pharmacokinetics
Pharmacology. Drug treatments
Polysaccharides - administration & dosage
Polysaccharides - chemistry
Polysaccharides - pharmacokinetics
Rat
Rats
Rats, Sprague-Dawley
Tumors
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Summary: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.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2004.05.013