Glucosamine binding to proteins in plasma and synovial fluid and blood cell/plasma partitioning in mouse and man in vitro.
Protein binding of [14C]glucosamine (400, 1000 and 4000 ng/ml) was evaluated in human and mouse plasma and in human synovial fluid. Blood cell/plasma partitioning in human and mouse was also determined. There was no measurable protein binding of [14C]glucosamine. Its association with human and mouse blood cells ranged from 43-47% and from 27-29%, respectively. Therefore, the unbound (pharmacologically active) fraction of glucosamine in plasma and at the site of action (the joint) is the same. Protein binding displacement drug-drug interactions are unlikely during the clinical use of crystalline glucosamine sulfate. No corrections are needed, either for unbound fraction when comparing human and mouse pharmacokinetic data or for blood cell/plasma partitioning to assess glucosamine total blood clearance from plasma data in these two species.
Persiani
Stefano
S
Rottapharm SpA, Monza, Italy. stefano.persiani@rottapharm.com
Matthews
Anne
A
Larger
Patrice
P
Hall
Michael
M
Rotini
Roberto
R
Trisolino
Giovanni
G
Antonioli
Diego
D
Zaccarelli
Lorenzo
L
Rovati
Lucio C
LC
D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D001800:Blood Specimen Collection / Q000379:methods; D004347:Drug Interactions; D004355:Drug Stability; D005944:Glucosamine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D010949:Plasma / Q000378:metabolism; D011485:Protein Binding; D013582:Synovial Fluid / Q000378:metabolism*
D001798:Blood Proteins; D005944:Glucosamine