MECHANISM OF PHARMACODYNAMIC AND PHARMACOKINETIC INTERACTIONS BETWEEN ACETOHEXAMIDE AND PHENYLBUTAZONE IN RABBITS

The interaction of acetohexamide (AH) with phenylbutazone (PBZ) was investigated in rabbits. Orally administered PBZ caused a potentiation of hypoglycaemic action after oral administration of AH. This can be explained by the fact that the co-administration of PBZ significantly increased both the serum concentrations of AH and its pharmacologically active metabolite, (-)-hydroxyhexamide [(-)-HH], after AH administration. The co-administration of PBZ decreased the renal clearance (Cl(r)) and non-renal clearance (Cl(nr)) of AH. PBZ inhibited the in vitro reduction of AH to (-)-HH and decreased the accumulation of (-)-HH by the kidney cortical slices. These results indicate that the mechanism of in vivo interaction of AH with PBZ is complicated.