Plasma protein binding of alpidem in healthy volunteers, in neonates and in liver or renal insufficiency.
The binding of alpidem, a new anxiolytic drug, has been studied in plasma from 6 healthy subjects, 12 patients with renal failure, 12 patients with liver cirrhosis and 12 chronic uraemics maintained on haemodialysis, as well as in 12 serum samples from the placental cord, to represent the situation in the newborn. The unbound fraction was 0.61% (healthy volunteers), 1.31% (newborns), 0.86% (cirrhotic patients), 0.72 (patients with renal failure), 0.70% (before haemodialysis) and 0.79% (after haemodialysis). Binding in the volunteers was significantly different from that in neonates and cirrhotics only. Alpidem became bound to isolated albumin (45 g.l-1) and alpha 1-acid glycoprotein (0.75 g.l-1) to 97.2% and 97.1%, respectively. The bound fraction of the drug in a mixture of two proteins was 99.1%. For alpidem, it appears that alpha 1-acid glycoprotein may balance the effect of any decrease in the albumin concentration.
Pacifici
G M
GM
Department of General Pathology, Medical School, University of Pisa, Italy.
Bianchetti
G
G
Viani
A
A
Rizzo
G
G
Carrai
M
M
Allen
J
J
Morselli
P L
PL
D000328:Adult; D000368:Aged; D014151:Anti-Anxiety Agents / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000097:blood*; D007231:Infant, Newborn / Q000097:blood*; D007674:Kidney Diseases / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism; D008107:Liver Diseases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011725:Pyridines / Q000097:blood*; D006435:Renal Dialysis
D014151:Anti-Anxiety Agents; D001798:Blood Proteins; D007093:Imidazoles; D011725:Pyridines; C052036:alpidem