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 (Clr) and non-renal clearance (Clnr) 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.
Imamura
Y
Y
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Nomura
T
T
Katsuki
Y
Y
Kojima
Y
Y
Otagiri
M
M
D000092:Acetohexamide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D004347:Drug Interactions; D007003:Hypoglycemia / Q000188:drug therapy; D007672:Kidney Cortex / Q000033:anatomy & histology / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D010653:Phenylbutazone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits
D001786:Blood Glucose; D001798:Blood Proteins; D010653:Phenylbutazone; D000092:Acetohexamide