Sulfadimethoxine-bucolome interaction in rabbits: role of N4-acetylsulfadimethoxine, a major metabolite of sulfadimethoxine.
The role of N4-acetylsulfadimethoxine (N4-AcSDM), a major metabolite of sulfadimethoxine (SDM), in protein binding and pharmacokinetic interactions between SDM and bucolome (BCP) was investigated in rabbits. When SDM and BCP were intravenously co-administered, BCP indirectly reduced the serum protein binding of SDM by causing a marked increase of N4-AcSDM concentration in serum, and significantly increased the steady-state volume of distribution (Vss) and total body clearance (C1tot) of SDM. In addition, the co-administration of N4-AcSDM was found to increase Vss and C1tot of SDM. These results lead us to conclude that N4-AcSDM plays an important role in protein binding and pharmacokinetic interactions between SDM and BCP in rabbits. Several investigations have demonstrated that a metabolite plays an important role in drug-drug interaction. For example, Sellers et al. (1) reported that when warfarin and chloral hydrate are co-administered, a major metabolite of chloral hydrate, trichloroacetic acid, reduces the plasma protein binding of warfarin and enhances its anti-coagulant activity. Our previous paper (2) showed that probenecid indirectly reduces the plasma protein binding of sulfadimethoxine (SDM) by causing a marked increase in the plasma concentration of N4-acetylsulfadimethoxine (N4-AcSDM), which is a major metabolite of SDM (3) and strongly displaces SDM from its plasma protein binding sites (2). However, as yet the role of this metabolite in drug-drug interaction has not been fully examined.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D008297:Male; D011485:Protein Binding; D011817:Rabbits; D013412:Sulfadimethoxine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics
D001463:Barbiturates; C038180:N(4)-acetylsulfadimethoxine; D013412:Sulfadimethoxine