Pharmacokinetics of a sulphamethoxazole/trimethoprim formulation in pigs after intravenous administration

Summary Plasma disposition, metabolism, protein binding and renal clearance of sulphamethoxazole (SMZ) and trimethoprim (TMP) were studied in four pigs after intravenous administration at a dose of 40 and 8 mg/kg, respectively. SMZ and TMP were quickly eliminated (mean elimination half‐lives: 2.7 and 2.4 h, respectively). SMZ was predominantly acetylated; no hydroxy and glucuronide derivates could be detected in plasma and urine. TMP was 0‐demethylated into 4‐hydroxytrimethoprim (M1) and 3‐hydroxytrimethoprim (M4) metabolite and subsequently extensively glucuronidated. SMZ, TMP and its M1 metabolite were excreted predominantly by glomerular filtration, while N4‐acetylsulphamethoxazole and glucuronide conjugates of the M1 and M4 metabolites of TMP were actively eliminated by tubular secretion. The proportional drug percentage being present in the urine as parent compound was 13.1% for TMP and 16.0% for SMZ. The glucuronide conjugates of the M1 and M4 metabolites formed the main part (81.5%) of urinary TMP ...