Distribution of moricizine in human blood: binding to plasma proteins and erythrocytes.
Using equilibrium dialysis and incubation experiments, we determined the binding of moricizine to human plasma, isolated plasma proteins, and erythrocytes. The mean (% +/- SD) plasma protein binding at various moricizine concentrations ranged from 81.2 +/- 2.1 to 89.9 +/- 2.1%. There was no apparent relationship between drug concentration and extent of binding in pooled plasma over the concentration range tested. However, protein concentration-dependent binding was observed with albumin and alpha 1-acid glycoprotein (alpha 1-AGP). The unbound fraction of moricizine fell from 61 to 19% and from 70 to 17% with increasing albumin (5 and 50 g/L, respectively) and alpha 1-AGP (0.2 and 1.2 g/L) concentrations. The binding of moricizine to beta-lipoprotein (5 g/L) was 70.6 +/- 3.1% and to gamma-globulin (12 g/L) was 13.6 +/- 3.3%. Moricizine partitioned into erythrocytes, showing an erythrocyte/plasma drug concentration ratio of 1.325 +/- 0.070 and erythrocyte/buffer ratio of 8.561 +/- 0.620. An estimation could be made that 57% of total drug in whole blood was associated with erythrocytes, 39% bound to plasma proteins, and 4% was free. The results of this study demonstrated that erythrocytes, albumin, and alpha 1-AGP were the major binding components in blood.
Department of Pharmacology, Shanghai Medical University, People's Republic of China.
J M
JM
Yang
K
K
Chan
W T
WT
Chiang
D001798:Blood Proteins / Q000378:metabolism*; D003956:Dialysis; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D016293:Moricizine; D009961:Orosomucoid / Q000378:metabolism; D010640:Phenothiazines / Q000097:blood* / Q000493:pharmacokinetics; D011485:Protein Binding; D005719:gamma-Globulins / Q000378:metabolism
D001798:Blood Proteins; D008077:Lipoproteins, LDL; D009961:Orosomucoid; D010640:Phenothiazines; D005719:gamma-Globulins; D016293:Moricizine