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).
Changes in disposition kinetics of sulphadimidine in response to acute regional liver damage in sheep.
Disposition kinetics of sulphadimidine in sheep, before and after regional liver damage by allyl alcohol, was investigated following a single IV injection (100 mg/kg). Allyl alcohol (12 mg/kg) provoked periportal liver lesion in 60 per cent of the animals. In normal sheep the mean elimination half-life of sulphadimidine was 7.47 +/- 1.09 hours. Liver damage significantly increased this value to 11.68 +/- 1.09 hours. Liver damage by allyl alcohol significantly changed the total body clearance (C1B), the overall elimination rate constant (beta) and the micro-constants k12 and kCl. The apparent volume of distribution (Vd) and the micro-constant k21 were not influenced by liver damage. The mean minimum steady-state concentration (Cp[min]) in normal sheep (38.43 micrograms/ml at 24 hours of interval) was found to be higher than previously reported. Liver intoxication significantly increased this value to 94.38 micrograms/ml. It is suggested that the regional liver damage has affected both the elimination and biotransformation of sulphadimidine.
Evaluation and Control of Collapsible Soils
Some compacted soils wetted under certain conditions of compaction and loading may exhibit additional settlement (collapse). To investigate the effect of the soil type, compaction water content, initial dry unit weight and applied pressure at wetting on collapse potential, 138 single‐oedometer tests were conducted on eight different soils. The results indicate that well‐graded soils tend to collapse more than poorly graded ones under similar conditions. Furthermore, collapse potential decreases with an increase in (1) The difference between the sand and clay percentages; (2) compaction water content; and (3) initial dry unit weight, while it increases with pressure at wetting. A multiple regression analysis was performed on the laboratory results to provide a collapse‐predictive model that was substantiated by data reported by several researchers. A chart is presented to estimate (1) The collapse potential of soils under various conditions; and (2) the critical water content beyond which no collapse is ex...