In vitro binding study of gemfibrozil to human serum proteins and erythrocytes: interactions with other drugs.
The binding of gemfibrozil to human serum, isolated proteins and erythrocytes was studied in vitro by equilibrium dialysis. Our results show that this drug is highly bound to serum (99%) at therapeutic levels. Human serum albumin was shown to be mainly responsible for this binding (98.6%) with a saturable process characterized by two binding sites with a moderate affinity. Like many acidic drugs with a carboxylic acidic group, gemfibrozil showed none or negligible binding to alpha 1 acid glycoprotein, lipoproteins and gamma-globulins. The drug binding to erythrocytes is very low (0.8%). The unbound fraction in blood remains constant (0.8%) within the range of therapeutic concentrations. Moreover, interactions were studied with bilirubin and palmitic acid at pathophysiological concentrations and acenocoumarol, salicylic acid, valproic acid, furosemide, phenylbutazone, tolbutamide, warfarin and sulfamethoxazol at therapeutic concentrations. Neither endogenous compounds nor the other drugs studied altered gemfibrozil binding in serum. Likewise, the binding of warfarin to serum and to human serum albumin (600 microM) is not influenced by gemfibrozil.
Hamberger
C
C
Barre
J
J
Zini
R
R
Taiclet
A
A
Houin
G
G
Tillement
J P
JP
D001798:Blood Proteins / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D015248:Gemfibrozil; D006801:Humans; D008433:Mathematics; D010421:Pentanoic Acids / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism; D014631:Valerates / Q000378:metabolism*
D001798:Blood Proteins; D010421:Pentanoic Acids; D012709:Serum Albumin; D014631:Valerates; D015248:Gemfibrozil