Pharmacokinetics, metabolism and renal clearance of sulphatroxazole in calves and cows

Abstract

The pharmacokinetic analysis of plasma concentration--time curves after a single i.v. dose of 20 mg/kg sulphatroxazole (STZ) to calves and cows revealed a small distribution volume of STZ (mean VD(area) = 0.22-0.26 l/kg) and an age dependent elimination (mean t1/2 6.6-18.8 h). In calves and cows, STZ was extensively metabolized into the N4-acetyl and 5-hydroxy derivatives. In the plasma of calves, the N4-acetyl metabolite (N4-STZ) was present in greater amounts than the hydroxy metabolite (5-OH-STZ), while in cows' plasma concentration of these two metabolites were similar. In the milk of dairy cows STZ concentrations paralleled those of the metabolites and were approximately 21 times lower than corresponding plasma concentrations. The mean plasma protein binding of STZ and its metabolites ranged from 36.4 to 82.5% of total concentration. The N4-STZ derivative was excreted by tubular secretion; the 5-OH-STZ and the parent compound, mainly by glomerular filtration. In calves the majority of STZ administered was excreted as N4-STZ (40-52%), while in cows the parent drug dominated the urinary excretion (36%).

Effects of age on the pharmacokinetics of single dose sulfamethazine after intravenous administration in cattle

“…In our study, V ss did not differ significantly among different age groups, which is in agreement with the results obtained by Nouws et al (1989) in calves of 12 and 18 weeks old.…”

“…Non-ionized drugs and those with good lipid solubility, pass in either direction across rumen epithelium by a passive diffusion mechanism (Atef et al 1981;Pulido et al 1998). Nouws et al (1989) administered sulfamethazine in ruminants of two different ages (twelve and eighteen weeks-old) and they observed a longer persistence of sulphadimidine at eighteen weeks-old compared to the twelve weeks-old calves (a lower total body clearance and a prolonged elimination of this drug were found in the older animals). These authors attribute this behaviour to significant reduction in sulphadimidine hydroxylation in the older calves.…”

Pharmacokinetics of sulphamethoxazole in calves and cows

“…The absence of hydroxylation of SMZ in ruminants is in sharp contrast to the extensive hydroxylation of sulphatroxazole and the pyrimidine sulphonamides (like sulphadimidine, sulphamerazine, sulphadiazine) in these animals (9,10). In cows sulphatroxazole is hydroxylated and acetylated to the same extent (10).…”

“…In cows sulphatroxazole is hydroxylated and acetylated to the same extent (10). Sulphamethoxazole and sulphatroxazole differ only in a methyl substituent at the 4 position of the oxazoyl side chain.…”

“…Blood (and milk) sampling occurred during 48 h and urine sampling during 12 h. SMZ and its metabolites 5-hydroxy-(SOH) and Neacetylsulphamethazole (N4-synthesised by Dr. Vree as described previously (14). Protein-binding studies and deglucuronidation of samples were carried out as described in earlier papers (9,10) The plasma sulphamethoxazole (SMZ) concentration-time curves could be * Plasma percentage of N4-SMZ versus SMZ in the final elimination phase analysed according to a two-compartment model. In newborn calves the total body clearance (C1B) was less than in adults (30-50%).…”