Impaired Oxidation of Antipyrine in Stagnant Loop Rats

Abstract

The drug-metabolizing capacity of the liver was assessed in rats with experimental stagnant loop syndrome. Self-filling stagnant loops were created surgically in the upper jejunum. The capacity to metabolize foreign compounds by oxidation and conjugation was assessed in vivo after dosing of ¹⁴C-antipyrine and ³H-paracetamol. The rate of antipyrine metabolism was also tested in stagnant loop rats treated with lincomycin and in control rats with some of the features of the stagnant loop syndrome. Four weeks after the operation the biological half-life of antipyrine was increased by 78% compared with controls, and the metabolic clearance was decreased by 38%. Lincomycin treatment prevented the impairment of antipyrine metabolism in stagnant loop rats. Neither anemia, reduced food intake after a sham-operation, nor simple phenol ingestion changed antipyrine half-life of control rats. Phenobarbital treatment increased the metabolic clearance of antipyrine in stagnant loop rats, but post-treatment clearance values were reduced by 35% compared with controls. The biological half-life and metabolic clearance of paracetamol were not significantly changed in stagnant loop rats. The results suggest a decreased rate of oxidative metabolism and a normal rate of conjugative metabolism in stagnant loop rats. Lincomycin-sensitive bacteria seem to be involved in the processes leading to impairment of drug oxidation in stagnant loop rats by an unknown mechanism.

Key-words:

• Antipyrine
• blind loop syndrome
• drug metabolism
• lincomycin
• paracetamol
• pharmacokinetics
• phenobarbital