Pharmacokinetics of three sulphonamides in ruminant and preruminant kids.
The pharmacokinetic properties of three sulphonamides were determined in ruminant and preruminant kids after oral and intravenous administration. First, sulphisomidine (SIM, 50 mg kg-1) and sulphadoxine (SDX, 30 mg kg-1) were given to seven kids, 10 to 12 weeks old, while on a milk replacer diet and again at 15 to 18 weeks when fed roughage. Secondly, SIM (100 mg kg-1) and sulphadimidine (SDD, 100 mg kg-1) were given at six to nine, 12 to 15 and 18 to 21 weeks old to eight kids, of which four were fed milk replacer and four were with their mothers (with access to roughage) until 15 weeks, after which all were fed roughage only. SDX and SDD exhibited non-linear (or capacity limited) absorption after oral dosage, suggesting possible active absorption mechanisms, and both drugs also showed non-linear elimination. Intravenous curves for SDD and SIM indicated that recycling occurred. With SDX, ruminant kids showed poorer systemic availability after oral dosage, shorter t1/2(el) and higher B than did preruminants. For SDD, ruminant kids had lower Vd and higher B than preruminants. SIM's t1/2(el) tended to shorten and beta to increase in both groups throughout the experiment. Not all differences between ruminants and preruminants in sulphonamide pharmacokinetics could be explained by the accumulation of acidic forestomach contents and the change of urine pH from acid to alkaline in the maturing ruminant. Other potential contributing factors require investigation, including possible alterations in hepatic drug metabolism. Of the three drugs tested, SDX might be the most satisfactory for therapeutic use in preruminant animals, because it has good bioavailability after oral administration and long t1/2(el).
Concentrations of sulfadoxine and trimethoprim in plasma, lymph fluids and some tissues 24 h after intramuscular administration to Angora goats.
This study was carried out to determine the concentrations of sulfadoxine and trimethoprim in plasma, lymph, and some tissues in goats after administration of a single recommended therapeutic dose. Five healthy, adult Angora goats were used. The drug combination, containing 200 mg sulfadoxine and 40 mg trimethoprim per millilitre, was given as a single IM injection at the recommended dose level, 15 mg/kg body weight for sulfadoxine and 3 mg/kg body weight for trimethoprim. The goats were slaughtered 24 hours after drug administration and samples were taken from liver, bone marrow, pelvic limb muscles, hepatic, thoracic duct, and the pelvic limb lymph fluids for analysis of drug concentrations by HPLC. The concentrations of trimethoprim in bone marrow, liver, pelvic limb muscles, hepatic lymph, the pelvic limb lymph, and thoracic duct lymph were found to be 6, 5, 4, 2, 5 and 15 times higher than those of plasma, respectively. Although the sulfadoxine concentrations in bone marrow, pelvic limb muscles, and liver were 2, 3 and 2 times higher than the plasma concentrations, respectively, the sulfadoxine concentrations in hepatic lymph, the pelvic limb lymph, and thoracic duct lymph were lower than those of plasma. The results show that the trimethoprim concentrations in lymph fluids were quite similar to those in tissues. However, the sulfadoxine concentrations in lymph fluids were different in each tissue.
Comparative observations of fever and associated clinical hematological and blood biochemical changes after intravenous administration of staphylococcal enterotoxins B and F (toxic shock syndrome toxin-1) in goats
The present investigation was undertaken to examine the characteristics of purified toxic shock syndrome toxin-1 (staphylococcal enterotoxin F) given intravenously to dwarf goats (dose, 0.02 to 20 micrograms kg-1). Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and hematological values were studied and compared with the changes seen after intravenous administration of staphylococcal enterotoxin B (dose, 0.02 to 0.5 micrograms kg-1). Similar changes such as fever, tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lymphopenia, and a decrease in serum alkaline phosphatase activity were observed. In contrast to the effects of toxic shock syndrome toxin-1, staphylococcal enterotoxin B induced colic, watery diarrhea with pseudomembranes, hemoconcentration, and a more pronounced increase in blood urea nitrogen. The results obtained demonstrate that (i) in the goat staphylococcal enterotoxin B is much more potent than toxic shock syndrome toxin-1 and (ii) the goat is a useful model to study the gastro-intestinal effects caused by staphylococcal enterotoxin B. The present finding that no clear relationship could be found between the temperature response and the alterations in zinc and iron levels in plasma support the theory that the febrile reactions and the changes in plasma trace metals are mediated by different polypeptides released by activated macrophages.