Pharmacokinetics, safety and tissue residues of sustained‐release sulfamethazine in sheep

Abstract

Concentration-time profiles and the rates of absorption, extent of distribution and half-lives of sulfamethazine (SMZ), administered intravenously, orally as a water solution and as a sustained-release formulation (CalfSpan) were determined in 10 healthy sheep. The geometric mean half-life of elimination of i.v. SMZ was 10.8 h, compared to 14.3 h for the sustained-release preparation (CalfSpan) and 4.3 h for the oral water solution. Blood levels of SMZ were at or above 50 micrograms/ml for more than 48 h for CalfSpan, for 24 h after i.v. SMZ (100 mg/kg body wt), and for less than 24 h after p.o. SMZ (100 mg/kg body wt). The mean bioavailability of the oral SMZ solution was 58.3% (AUCp.o./AUCi.v.). The estimated bioavailability of the CalfSpan preparation was 52.5%. The safety of the sustained-release preparation was tested by dosing sheep with multiples (one, three and five times) of the recommended dose (one tablet, 8 g SMZ, per 20 kg body wt), once a day for 3 days. Clinical blood chemistries showed a significant increase in serum iron, and a decrease in serum phosphorus in animals treated at the 3x and 5x dose levels. Necropsies of the 5x dose animals did not show any gross signs that could be attributed to SMZ, and histological examination of tissues from the 5x animals revealed no organ pathology. Residues of SMZ in liver, fat, kidney and skeletal muscle were measured in 20 animals that received one bolus per 20 kg body wt. The results indicate that SMZ residues are cleared rapidly, and are at or below the tolerance level of 0.1 mg/kg within 8 days after dosing so that the 18-day withdrawal time used in cattle would provide an appropriate margin of safety if used in sheep.

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

“…The value of V ss is similar to those previously described in ruminant species (Witkamp et al 1992;Witkamp et al 1992;Bulgin et al 1991;Baroni et al 2007). 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.…”

Comparison of bovine in vivo bioavailability of two sulfamethazine oral boluses exhibiting different in vitro dissolution profiles

“…Interestingly, both in our investigation and in the study of Bulgin et al. (1991), quantifiable drug concentrations were seen in the blood within 15 min following the administration of the oral solution.…”

“…Along a similar line, marked differences in oral bioavailability and elimination T 1/2 were seen when sulfamethazine was administered as either an i.v. bolus, an oral solution or a sustained release bolus to sheep (Bulgin et al. , 1991).…”

“… Profiles of various sulfamethazine preparations in sheep. Based upon work from Bulgin et al. (1991).…”

Investigation on the Counteracting Effect of Spirulina Against Potentated Sulfonamide’s (Cotrim Ds®) Side Effects in Rat

“…These have adverse reactions in elderly patients including severe skin reactions, generalized bone marrow suppression and decreased platelets (Agarwal, 1992). Moreover, these have gastrointestinal side effects (Bulgin et al, 1991), hypersensitivity side effects (Noli et al, 1995), hematologic side effects (Weiss and Adams, 1987), renal side effects (Duffee et al, 1984) and hepatic side effects (Twedt et al, 1997).…”