The effect of water deprivation on the pharmacokinetics of antipyrine and sulphadimidine following intravenous administration in Nubian goats

The effect of water deprivation on the pharmacokinetic parameters of antipyrine and sulphadimidine in the Nubian goat was studied. Water deprivation, to a level of dehydration at which the animals lost an average of 7.5% body weight, resulted in a significant reduction in antipyrine clearance (p<0.05), and a consequently increased AUC value (p<0.05). No effect was observed on the distribution parameters of the drug. In dehydrated animals which had lost an average of 10% or 12.5% of their body weight owing to water deprivation, significant changes were found in the distribution and elimination pharmacokinetic parameters of antipyrine and sulphadimidine. The volume of distribution was significantly decreased, resulting in elevated plasma levels for the two drugs compared to normally watered animals. Significant decreases in clearance and subsequent prolongation of the elimination half-lives were observed during these periods of water deprivation. These changes in the disposition kinetics of the two drugs may be attributed to the loss of total body water and extracellular fluids and changes in the liver and kidney functions taking place during dehydration.     

Pharmacokinetics of antipyrine and sulphadimidine (sulfamethazine) in camels, sheep and goats

The pharmacokinetics of antipyrine and sulphadimidine were studied in male camels, sheep and goats. The two drugs were administered concomitantly. Following intravenous injection of antipyrine (25 mg/kg) and sulphadimidine (sulfamethazine) (100 mg/kg), the pharmacokinetics of the two drugs were adequately described by a one-compartment model. Antipyrine half-life in goats (2.58 h) was shorter than that in sheep (4.04 h) and camels (18.78 h). The plasma clearance was greatest in goats then sheep and then camels. For sulphadimidine, a significantly greater volume of distribution was observed in camels and the greatest plasma clearance and shortest half-life were reported in goats. Sulphadimidine half-life was 2.77 h in goats, 4.72 h in sheep and 7.36 h in camels. The present results suggest that goats have the fastest elimination of these drugs from the circulation, followed by sheep and then camels.     

The effect of testosterone on the plasma disappearance rates of sulphadimidine and antipyrine in castrated dwarf goats

Summary

Plasma disappearance of sulphadimidine and antipyrine was studied in adult castrated dwarf goats before and following pretreatment with testosterone. Comparison was made with entire males before and after castration. Testosterone pretreatment caused a significant increase in the apparent‐ elimination half‐life in castrates, whilst in entire males castration caused a significant decrease.     

The effect of testosterone on the plasma disappearance rates of sulphadimidine and antipyrine in castrated dwarf goats

Plasma disappearance of sulphadimidine and antipyrine was studied in adult castrated dwarf goats before and following pretreatment with testosterone. Comparison was made with entire males before and after castration. Testosterone pretreatment caused a significant increase in the apparent elimination half-life in castrates, whilst in entire males castration caused a significant decrease.     

The effects of fascioliasis on the activities of some drug-metabolizing enzymes in desert sheep liver.

Desert sheep experimentally or naturally infected with Fasciola gigantica were used to study the influence of infection on the activities of some drug-metabolizing enzymes found in the liver. The enzymes investigated were aminopyrine N-demethylase, aniline 4-hydroxylase and UDP-glucuronyltransferase. The experimental infection was confirmed histologically by detection of Fasciola eggs in faeces and by measuring the activities of sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST) in plasma during the course of the disease. Liver specimens from naturally infected sheep were obtained from the slaughter house. The activities of aminopyrine N-demethylase and aniline 4-hydroxylase were significantly decreased in sheep either naturally infected or during the acute stage of experimental fascioliasis (killed 5 weeks post-infection). The activity of UDP-glucuronyltransferase was decreased in naturally infected sheep and those killed 9 or 13 weeks post-experimental infection.     

The effect of testosterone and rutting on the metabolism and pharmacokinetics of sulphadimidine in goats

After testosterone pretreatment of castrated goats and during the rutting season of adult entire male goats, the oxidative metabolism of sulphadimidine (SDM) was inhibited markedly compared with the castrated control state of these animals. The oxidation of the 5 position (yielding 5-hydroxysulphadimidine) and of the 6-hydroxymethyl group (yielding 6-carboxysulphadimidine) was decreased equally, with that of the methyl group at the pyrimidine side chain itself being 6-hydroxymethylsulphadimidine (CH2OH), whereas the acetylation pathway was unaffected by testosterone. The consequence of altered metabolism by testosterone was a prolongation of SDM presence in the body. Effects on protein binding of the CH2OH metabolite and on the renal clearance of SDM were also investigated.     

Effect of age on the pharmacokinetics of antipyrine in calves

Single doses of 15 mg kg⁻¹ antipyrine were given intravenously to 10 female calves of the black and white breed at one, two, four, six, eight and 12 weeks of age, and the concentrations of antipyrine, 4-hydroxyantipyrine (4-oha), 3-hydroxymethylantipyrine (hma) and norantipyrine (nora) were measured in plasma and urine by high performance liquid chromatography. The first three months of life were characterised by a steady decrease in the apparent volume of distribution (aV_d) and half-life (t_0.5) of antipyrine. The systemic clearance (Cl_s) of antipyrine per unit bodyweight increased significantly between one and 12 weeks of age. Age did not influence the excretion of hma and nora in urine, but the excretion of 4-oha by 12-week-old calves was significantly greater than by one-week-old calves. There was an age-related change in the partial clearances of the antipyrine metabolites when expressed per unit bodyweight.     

Pharmacokinetics and urinary excretion of sulphadimidine in sheep and goats

Pharmacokinetics and urinary excretion of sulphadimidine were determined in sheep and goats following a single intravenous injection (100 mg/kg). The disposition of the drug was described in terms of exponential expression: C _p= Be ^-βt. Based on total (free and bound) sulphonamide level in plasma, pseudo-distribution equilibrium was rapidly attained and the half-life for elimination was 3.88 ± 0.64 h and 4.00 ± 0.34 h in sheep and goats, respectively. Body clearance, which is the sum of all clearance processes was 88 ± 19 and 55 ± 4 ml/kg/h in sheep and goats. Based on this study a satisfactory intravenous dosage regimen might consist of 100 and 60 mg sulphadimidine/kg body wt for sheep and goats and should be repeated at 12 h intervals. The influence of disease conditions on predicted plasma levels remain to be verified experimentally. Three-quarters of an intravenously injected dose of sulphadimidine was excreted in the urine of sheep and goats within 24 h of administration. The drug was mainly excreted as free amine while acetylated drug constituted 7 and 8% of total drug content in the urine of sheep and goats, respectively.     

The effect of niclofolan on desert sheep experimentally infected with immature Fasciola gigantica

Eight desert sheep were each infected orally with 500 metacercariae of Fasciola gigantica and, after 4 weeks, four of the animals were given niclofolan orally at the recommended therapeutic dose rate of 7 mg/kg, the other four remaining as controls. One week later, the animals were slaughtered and the fasciocidal effect of the drug was evaluated on the basis of worm burden, haemogram, some plasma constituents, and gross and histopathological lesions of the liver, as indicators of efficacy. The treatment was found to be ineffective, the degree of infection remaining the same as in the untreated control group. The experiment was repeated using eight infected sheep: four were given the drug orally at a dose rate of 10.5 mg/kg, i.e., 1.5 times the recommended dose; and the same parameters were measured as described above. The drug failed to cure the infected sheep, and caused depression, anorexia and weakness. In a third experiment six sheep were infected as before and three were treated with niclofolan by deep i.m. injection at the recommended therapeutic dose of 2 mg/kg. A week later the animals were killed and examined as before. The drug was effective in treating the infection and produced no untoward effects except for transient signs of pain at the site of injection. It seems possible that the oral dose, unlike the i.m. dose, of niclofolan is not absorbed and/or metabolized sufficiently to prevent elimination of the infection.     

牛羊肝片吸虫病的诊断与治疗

2006年10月甘肃省肃南县皇城镇北峰村和西城村的5户牧民饲养的甘肃高山细毛羊部分羊只胸腹出现水肿,个别母羊流产,死亡两只,经检查初步诊断为羊肝片吸虫病。