Protein binding kinetics of @entity6186 (LM) and @entity3402 (CM) were studied using plasma, albumin and alpha 1-acid glycoprotein (AGP) derived from @entity1 , @entity235 , @entity291 and @entity742 . Based on Rosenthal plots of LM and CM, drug-binding property in plasma presented specific and non-specific binding, except for LM in @entity291 and @entity742 and for CM in @entity742 , where only non-specific binding was demonstrated. Dissociation constant (Kd) and binding capacity (Bmax) for specific binding and proportionality constant (PC) for non-specific binding were as follows: Kd = 3.14 mumol/L, Bmax = 15.28 mumol/L, PC = 0.19 for @entity1 ; Kd = 3.84 mumol/L, Bmax = 6.55 mumol/L, PC = 0.14 for @entity235 ; PC = 0.12 for @entity291 ; PC = 0.16 for @entity742 in LM and Kd = 0.94 mumol/L, Bmax = 12.24 mumol/L, PC = 4.98 for @entity1 ; Kd = 1.48 mumol/L, Bmax = 9.52 mumol/L, PC = 2.91 for @entity235 ; Kd = 1.22 mumol/L, Bmax = 4.45 mumol/L, PC = 2.40 for @entity291 ; PC = 1.48 for @entity742 in CM. The specific binding for each species was different, showing more difference in Bmax compared with Kd. The non-specific binding of LM was similar among species whereas that of CM was different, implying species difference. The drug-binding property of AGP for each species was all specific binding and the Kd was comparable to that obtained from plasma, indicating that AGP is a major specific binder in plasma. The lack of detection of specific binding for LM in @entity291 and @entity742 and for CM in @entity742 plasma could be attributable to a higher Kd and lower plasma AGP concentration compared with other species. The drug-binding property of albumin was characterized as all non-specific, without a great difference among species. Except for CM in @entity742 , the lower PC in albumin solution compared with that in plasma suggested the presence of another non-specific binder in plasma, i.e. lipoprotein. From the simulation of drug-binding percentage to AGP concentrations, AGP could be a major contributor to drug-plasma protein binding in pathological states. The degree of AGP-drug binding for each species could vary according to the degree of increase of AGP concentrations from a healthy to a pathological state, inducing a decrease in the unbound fraction (fp): 6.1 fold for @entity235 , 4.6 fold for @entity1 , 1.8 fold for @entity742 and 1.4 fold for @entity291 in LM; 5.8 fold for @entity235 , 5.7 fold for @entity291 , 4.0 fold for @entity1 and 1.5 fold for @entity742 in CM. Therefore, the disposition and efficacy of @entity35995 affected by fp can be modified differently by the change of fp attributable to the alteration of plasma @entity14214 concentration in each species.

Contribution of alpha 1-acid glycoprotein to species difference in XXXX -plasma protein binding kinetics.

@entity1 :: ('9606', 'Species') :: ['humans'] @entity742 :: ('9940', 'Species') :: ['sheep'] @entity235 :: ('9615', 'Species') :: ['dogs'] @entity6186 :: ('MESH:D008034', 'Chemical') :: ['lincomycin'] @entity14214 :: ('CHEBI:73349', 'Chemical') :: ['AGP'] @entity291 :: ('9913', 'Species') :: ['cattle'] @entity3402 :: ('MESH:D002981', 'Chemical') :: ['clindamycin'] @entity35995 :: ('MESH:D055231', 'Chemical') :: ['lincosamides']
@entity35995 :: (MESH:D055231,Chemical) :: ['lincosamides']
