Effect of phenylbutazone on serum protein binding and pharmacokinetic behavior of sulfadimethoxine in rabbits, dogs and rats.
The effect of phenylbutazone (PBZ) on the in vitro binding of sulfadimethoxine (SDM) to serum or albumin was compared among rabbits, dogs and rats. In rabbits, a major metabolite of SDM, N4-acetylsulfadimethoxine (N4-AcSDM), markedly reduced the in vitro binding of SDM, and PBZ significantly increased the serum concentration of N4-AcSDM after SDM administration. PBZ did not affect the in vitro binding of SDM. These findings indicate that in rabbits, PBZ indirectly reduces the in vivo binding of SDM through the interaction of PBZ with N4-AcSDM. In dogs, both PBZ and N4-AcSDM caused the reduction in the in vitro binding of SDM. However, unlike rabbits, the contribution of N4-AcSDM to the in vivo binding of SDM appeared to be negligible in dogs. In rats, PBZ or N4-AcSDM had little effect on the in vitro binding of SDM. The co-administration of PBZ significantly increased the total body clearance and steady-state volume of distribution of SDM in rabbits. Such changes in pharmacokinetic behavior were not observed in dogs and rats.
Imamura
Y
Y
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Nakamura
H
H
Otagiri
M
M
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D004285:Dogs; D004347:Drug Interactions; D008297:Male; D010653:Phenylbutazone / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism; D013045:Species Specificity; D013412:Sulfadimethoxine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D001798:Blood Proteins; D012709:Serum Albumin; C038180:N(4)-acetylsulfadimethoxine; D013412:Sulfadimethoxine; D010653:Phenylbutazone