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).
Effect of tick-borne fever on the disposition of sulphadimidine and its metabolites in plasma of goats.
The effect of tick-borne fever (TBF) on the plasma disposition of sulphadimidine (SDM) and its metabolites in goats was studied. In uninfected goats, SDM was extensively metabolised mainly by hydroxylation, glucuronidation and to a minor extent by acetylation. In TBF infected goats the hydroxylation of SDM into 6-methylhydroxysulphadimidine (SCH2OH) as well as into 5-hydroxysulphadimidine (SOH) was markedly reduced (-57.6 and -63.6 per cent, respectively). An unidentified metabolite (metabolite X) was detected, which was largely glucuronidated in the uninfected goats. In the TBF infected goats the glucuronide derivatives of the X metabolite and of SOH were barely detectable. In TBF infected goats the plasma concentration of the N4-acetylated metabolite (N4-SDM) was decreased to a lesser extent (-22.1 per cent) than the hydroxy metabolites. Due to the diminished metabolism the elimination half-life of SDM was increased 1.8 times and the total sulphonamide body clearance was diminished compared with findings in the control experiments.
Clinical, haematological and blood biochemical changes in goats after experimental infection with tick-borne fever.
Tick-borne fever in goats caused by Ehrlichia (Cytoecetes) phagocytophila was characterised by high fever, dullness, anorexia, tachycardia and a slight to moderate inhibition of rumen motility. The animals developed a gradual decline in the total number of circulating white blood cells. There was a decrease in lymphocytes over a short period, followed by an increase. The number of neutrophils was higher on the 3rd day, causing considerable change in the lymphocyte:neutrophil ratios. The number of eosinophils increased slightly. Serum alkaline phosphatase (ALP) decreased during the febrile episodes, and a marked decline was observed in both plasma zinc and iron concentrations. Furthermore, there was a small but progressive decrease of haemoglobin and haematocrit values. Circulating endogenous pyrogen/leucocyte endogenous mediator could not be detected in plasma from febrile goats. Tick-borne fever was passively transmitted to kids with plasma obtained from these febrile animals.