| Abstrakt: |
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 (sun, 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. sdxand sddexhibited 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 sddand sdxindicated that recycling occurred. With sdx, ruminant kids showed poorer systemic availablity after oral dosage, shorter t½(el)and higher B than did preruminants. For sdd, ruminant kids had lower Vdand higher B than preruminants. sdx's t½(el)tended to shorten and ßto 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, sdxmight be the most satisfactory for therapeutic use in preruminant animals, because it has good bioavailability after oral administration and long t½(el). |
