Deacetylation as a determinant of sulphonamide pharmacokinetics in pigs

Abstract

SUMMARY Sulphamonomethoxine (SMM), sulphadimidine (SDD), sulphadiazine (SDZ) and their N4-acetyl derivatives (AcSMM, AcSDD and AcSDZ) were intravenously injected into Goettingen miniature pigs and deacetylation was evaluated from plasma concentration-time curves, renal excretion, and rate constants obtained from pharmacokinetic analysis, using a non-linear least-squares method. Deacetylated metabolite was detected in both plasma and urine after intravenous injection of AcSMM, AcSDD and AcSDZ. The area under the curve (AUC) values for the deacetylated metabolite were significantly higher than those for acetyl derivatives after AcSMM and AcSDD administration, but significantly lower after AcSDZ. After AcSMM and AcSDD injection, the concentration ratio between deacetylated metabolite and acetyl derivative was almost constant in the terminal linear phase and similar to that seen after injection of sulphonamide. After AcSDZ injection, however, a constant ratio was not observed. These results indicate that deacetylation can have a significant effect on the pharmacokinetics of SMM and SDD, but not on those of SDZ in pigs. The rate constant for deacetylation was significantly higher than that for acetylation for SMM and SDD, but significantly lower for SDZ. It is, therefore, concluded that deacetylation may be a determinant of the pharmacokinetics of SMM and SDD in pigs. It was, however, not a determinant of SDZ pharmacokinetics because N4-acetylation is not the main elimination route in pigs.

Determination of selected sulfonamide antibiotics and trimethoprim in manure by electrospray and atmospheric pressure chemical ionization tandem mass spectrometry

“…Trimethoprim is a synergist and N 4 ‐acetylsulfadiazine is a major metabolite of sulfadiazine in pigs 9,. 21…”