Disposition of sulfadimidine and its N₄‐acetyl and hydroxy metabolites in horse plasma

Abstract

Nouws, J.F.M., Vree, T.B., Baakman, M., Driessens, F., Smulders, A. & Holtkamp, J. Disposition of sulfadimidine and its N 4 ‐acetyl and hydroxy metabolites in horse plasma. J. vet. Pharmacol. Therap. 8, 303–311. The plasma disposition of sulfadimidine (SDM) and its metabolites N 4 ‐acetylsulfadimidine (N 4 ‐SDM), 6‐hydroxymethyl‐4‐methyl‐pyrimidine (SCH 2 OH) and 5‐hydroxy‐4,6‐dimethyl‐pyrimidine (SOH), was studied in three horses following intravenous administration of SDM at dose levels of 20 and 200 mg/kg in cross‐over trials. The percentages of N 4 ‐SDM (0.58‐0.90%), SOH (0.83‐6.75%) and SCH 2 OH (0.38‐0.71%) in plasma, expressed as a percentage of the total sulfonamide concentration, were small and their plasma concentrations were parallel with SDM from 4 h following administration. At high doses (200 mg/kg), the elimination half‐life was slightly longer than at low doses (6.0, 10.5, 11.0 vs 5.0 , 9.5, 9.5, respectively). The plasma protein binding was related to the dose; it was for the 20 and 200 mg/kg doses, respectively:SDM:61.5–73.3% and 50.5–52.1%; SOH: 47.1–71.0% and 36.7–39.5%, and for N 4 ‐SDM: 45.9–63.2% and 38.3–53.7%. The protein binding for SCH 2 OH, measured in samples obtained at the high dose level, ranged from 13.8 to 20.0%. Dr J. F. M. Nouws, RVV‐District 6, Wolfskuilseioeg 279, Nijmegen, Tlie Netherlands.