Effect of age on the acetylation and deacetylation reactions of sulphadimidine and N₄‐ acetylsulphadimidine in calves

Abstract

Following intravenous (i.v.) or intramuscular (i.m.) administration of sulphadimidine (SDM), the pharmacokinetics of SDM and N4-acetylsulphadimidine (N4-SDM) were studied in plasma of calves from the first day of life to the age of about 6 months. An obvious age dependency was observed for the elimination half-life (t1/2) of SDM: the first day of life the t1/2 ranged between 13.5 and 17 h, and decreased in approximately 3 weeks to 4-6 h and remained constant from this time. The metabolite N4-SDM, as a percentage of the total concentration of the sulphonamide measured in plasma of neonatal calves, ranged between 21.6 and 25.5% at the first day of life, declined in 3 weeks to approximately 12.8%, and at 5 till 9 weeks the final percentage was about 6.8%. Following administration of N4-SDM, the elimination half-life of N4-SDM was 3 h in an 8-day-old calf declined to 1.4-1.7 h in 4-week-old calves, and was 0.9 h in calves older than 11 weeks. The percentage of SDM (a metabolite of N4-SDM) in plasma increased with time after injection from 5.5 to 62.8% of the total sulphonamide plasma concentration. This value was age-related. The total body clearance of N4-SDM was three- to five-fold higher than that of SDM.

Pharmacokinetics and Metabolism of Sulphadiazine in Neonatal and Young Pigs

“…The elimination half-life of SDZ (t1,2P) was about 3 times longer during the first days of life than at 8 weeks at which time adult level was reached (Luther 1978). However, the significance of this difference as an index of altered elimination rate with age is not clear, since tl,2P is a hybrid parameter affected by changes in both distribution and elimination (Perrier & Gibaldi 1974). The change in Vdss of SDZ with age indicates that body clearance (CIS) is a better index for comparison of elimination in newborn and young animals.…”

Deacetylation as a determinant of sulphonamide pharmacokinetics in pigs

“…Therefore, the ratio of the intercept between sulphonamide and its acetyl derivative gives a mean value for the concentration ratio in the linear phase. This ratio was similar for the sulphonamide and its acetyl derivative, when expressed as the geometric mean (a SD range): 4.72 (2.94-7.57) and 5.38 (2.76-10.5) after SMM and AcSMM, respectively; 27.9 (24.5-31.9) and 24.5 (19.9-30.1) after SDD and AcSDD, respectively. The parallel decrease was not observed after injection of AcSDZ.…”

“…Althpugh many metabolic pathways have been identified for sulphonamides, and especially in ruminants hydroxylation is the main metabolic pathway (2,3,19), it is well recognized that the main elimination route is the acetylation followed by renal excretion through the active transport system in many species other than dogs (14). Shimoda et al de-Acetylated metabolites of sulphonamides are deacetylated to their parent compounds in many species, including pigs (7,11,12), calves (5), and humans (13,15,16). Since these animal species have an extensive acetylation capacity, deacetylation of acetylated metabolites of sulphonamides has been recognized to be a part of the acetylation-deacetylation equilibrium and therefore to be an important factor affecting sulphonamide pharmacokinetics.…”

“…Although isolated tibial fractures (i.e., with the fibula intact) account for 15% all canine and feline tibial fractures (11), little has been reported about their occurrence or their management, except that this is a common type of fracture in juvenile dogs (1,5,11). Owing to the internal splinting of the fractured tibia by the intact fibula, only slight axial and rotational dislocation of tibial fragments is observed on radiographs.…”

Bioavailability and pharmacokinetics of sulfamethazine in the pony

“…Thus, the horse may eliminate sulfamethazine in a manner similar to man and ruminants as these species have a rate limited step. Sulfamethazine's dosedependency in the species studied is due, in part, to a saturation of the metabolic process where the base drug is converted to its N4acetyl and hydroxy metabolites, a function complicated by both the maturity of the enzyme systems and the genetic characteristics of the individual (Olson et aL, 1978;du Souich et al, 1979;Van Gogh, 1980;Nouws et al, 1983;Nouws et al, 1986). The volume of distribution calculated by the area method (V, = 0.699 Vkg) was greater than the previously reported range of 0 .…”