丙硫咪唑缓释注射液对小鼠旋毛虫病的效果

试验采用１２０只小鼠，每只感染１１６条脱囊幼虫。用于治疗的９６只１１、鼠分为４×４组，分别按旋毛虫的４个不同发育阶段分别１次肌肉注射３０，５０，７５和１００ｍｇ·ｋｇ￣（－１）丙硫咪唑缓释注射剂，结果肠内脱囊期幼虫减少均为１００％；肠内成虫减少率分别为７９％，９０．３％，９４．３％和９９．２％；移行期幼虫减少率分别为８７．２２％，８９．９４％，９３．１６％和９５．２４％；成囊期幼虫减少率分别为９０．５％，９４．４８％，１００％和９４．１８％。各治疗组与对照组比较均有极显著差异。试验结果表明，按３０ｍｇ·ｋｇ￣（－１）～１００ｍｇ·ｋｇ￣（－１）剂量给小鼠１次肌肉注射丙硫咪唑缓释注射剂，对各发育阶段的旋毛虫均有显著的杀虫效果。使用该制剂具有用药量小，疗效高，给药次数少，使用安全等优点。     

丙硫咪唑在囊虫患者体内药代动力学的研究

用反相高效液相色谱法测定丙硫咪唑的中间代谢体丙硫咪唑亚砜和丙硫咪唑砜,在7名囊虫患者体内的血药含量及药代动力学研究,以含0.40％乙酸的光谱纯甲醇为流动相,以色谱柱MicrQ Bondpak CN 0.39×15cm 10μ为固定相,紫外检测器波长290nm,以甲苯咪唑为内标物亚砜收率为95.23±6.74％;砜收率为90.04％±5.32％。不同浓度水平测定结果,日内和日间变动系数均小于10％;以亚砜加砜为实测值的药代动力学符合有吸收因素二室模型。患者单剂量口服丙硫咪唑25mg/kg体重时,平均血药10h达峰,亚砜加砜之和为558.14±208.34ng/ml血;生物半衰期t_(1/2)β为13.54±3.11h;血浆清除率CLB为132.79±45.58L/kg·h。     

紫外分光光度法测定阿苯达唑片含量的不确定度评定

对紫外-可见分光光度法测定阿苯达唑片含量的不确定度进行评定以及测量过程中各种不确定度来源进行分析与评估,含量测定结果可表示为（95．7±2．0）％（k=2）。结果表明,仪器的吸光度、重量差异、称样量和移液管的体积引入的不确定度为测量结果不确定度的主要影响因素。     

Naphthalophos combinations with benzimidazoles or levamisole as effective anthelmintics for sheep

Objective: To investigate the relative efficacy and safety of the anthelmintic naphthalophos in sheep, either given alone or in combination with benzimidazole (fenbendazole and albendazole) or levamisole anthelmintics.
Design: A parasitological study using faecal egg count reduction tests, a validating slaughter trial and field safety trials.
Procedure: Faecal egg count reduction tests were carried out on 13 farms. Naphthalophos and combinations of naphthalophos with levamisole and fenbendazole were included in the drench tests. On one property a controlled efficacy study was carried out to validate faecal egg count reduction test findings. In this trial, sheep were slaughtered 10 days after treatment and the remaining parasites recovered from the gastro-intestinal tract. Safety trials were carried out on eight farms where approximately 50 000 sheep were treated with naphthalophos and albendazole that were tank mixed in the backpack.
Results: The efficacy of naphthalophos alone in faecal egg count reduction tests ranged from 59 to 98% with one test showing 95% reduction. The efficacy of naphthalophos and levamisole ranged from 74 to 100%, with 5 farms showing 95% reduction. The efficacy of naphthalophos and fenbendazole ranged between 88 and 100% with 95% reduction achieved on 10 farms. The controlled efficacy study showed a good correlation between the faecal egg count reduction tests and numbers of parasites recovered, except for Nematodirus where the faecal egg count reduction tests overestimated efficacy. The mortality rate in the safety trials was 0.05%, with most fatalities occurring on one farm.
Conclusion: The combination of naphthalophos and fenbendazole was more effective than a combination of naphthalophos and levamisole, and will provide a sufficiently safe drench rotation option.     

阿苯达唑和奥芬达唑对体外培养猪囊尾蚴能量代谢变化的影响

测定了在阿苯达唑和奥芬达唑作用下体外培养猪囊尾蚴磷酸烯醇式丙酮酸羧激酶（PEPCK）、丙酮酸激酶（PK）、延胡索酸还原酶（FR）、苹果酸酶（ME）活性的变化及葡萄糖（GLC）、乳酸（LAC）含量的变化。结果表明，2种药物作用均可在体外作用条件下显著改变未成熟期及成熟期猪囊尾蚴的能量代谢。提示，苯并咪唑氨基甲酸酯类药物的作用机理可能是通过干扰虫体能量代谢，阻断能量的产生，导致虫体死亡。     

用丙硫苯咪唑检测羊线虫抗药性的体外虫卵孵化试验

为探讨用丙硫苯咪唑进行体外虫卵孵化试验检测羊线虫对苯并咪唑类药物的抗药性,对23个羊场的25份田间样品用丙硫苯咪唑和噻苯咪唑进行了虫卵孵化试验并与先前减卵试验（faecal egg count re-duction test,FECRT）的结果比较。结果表明,25份样品中,丙硫苯咪唑和噻苯咪唑对受检虫卵的半数致死量（LD50）均值分别为0.050 1和0.054 0μg/mL,差异不显著。FECRT检测有抗药性的4个羊场,75%的样品对丙硫苯咪唑和噻苯咪唑的LD50均值均在0.1μg/mL以上,只有1个羊场的的LD50值分别为0.068 9μg/mL（丙硫苯咪唑）和0.071 2μg/mL（噻苯咪唑）。检测为可疑的2个羊场,其样品的LD50值为0.04～0.07μg/mL;FECRT检测敏感的蠕虫群体的LD50均在0.04μg/mL以下。此外,丙硫苯咪唑用纯的二甲基亚砜溶解和稀释后于4℃保存7 d,LD50值变化不大,提示药效无明显下降,而保存14 d后药效有下降趋势。     

The Effect of Anthelmintic Capsules on the Egg Output and Larval Viability of Drug-resistant Parasites

Challenge with an equal mix of drug-resistant and drug-susceptible larvae of Teladorsagia circumcincta resulted in infections in groups of lambs (n = 6) either untreated or given controlled-release capsules, containing either albendazole or ivermectin. Lambs treated with albendazole capsules contained similar numbers of adult worms at necropsy to the other groups but had no detectable faecal egg count. Animals treated with ivermectin capsules had similar worm burdens and faecal egg counts to the control group but the worms had significantly higher numbers of eggs in utero. These results provide evidence for suppression of egg production by both anthelmintic treatments. The observation that albendazole caused a significant reduction in the developmental success of parasite eggs also has implications for the use of faecal egg count as an indicator for pasture contamination with resistant parasites. In two further groups of lambs, either untreated or given albendazole capsules, treatment caused a significant reduction in egg count and adult worm burden of Trichostrongylus colubriformis. No significant effects were observed on in utero egg counts or egg viability and the apparent effect on the number of eggs produced in faeces per adult female was not significant (p = 0.077). There was, therefore, no evidence that albendazole controlled-release capsules caused suppression of egg output in this species.     

Aspects of the Pharmacokinetics of Albendazole Sulphoxide in Sheep

The plasma disposition kinetics of albendazole sulphoxide (ABZSO), ((+)ABZSO and (–)ABZSO) and its sulphone metabolite (ABZSO₂) were investigated in adult sheep. Six Corriedale sheep received albendazole sulphoxide by intravenous injection at 5 mg/kg live weight. Jugular blood samples were taken serially for 72 h and the plasma was analysed by high-performance liquid chromatography (HPLC) for albendazole (ABZ), ABZ sulphoxide (ABZSO) and albendazole sulphone (ABZSO₂). Albendazole was not detected in the plasma at any time after the treatment, ABZSO and ABZSO₂ being the main metabolites detected between 10 min and 48 h after treatment. A biexponential plasma concentration versus time curve was observed for both ABZSO and ABZSO₂ following the intravenous treatment. The plasma AUC values for ABZSO and ABZSO₂ were 52.0 and 10.8 (g.h)/ml, respectively. The ABZSO₂ metabolite was measurable in plasma between 10 min and 48 h after administration of ABZSO, reaching a peak concentration of 0.38 g/ml at 7.7 h after treatment. Using a chiral phase-based HPLC method, a biexponential plasma concentration versus time curve was observed for both ABZSO enantiomers. The total body clearance was higher for the (–) than for the (+) enantiomer, the values being 270.6 and 147.75 (ml/h)/kg, respectively. The elimination half-life of the (–) enantiomer was shorter than that of the (+) enantiomer, the values being 4.31 and 8.33 h, respectively. The enantiomeric ratio (+)ABZSO/(–)ABZSO at t ₀ was close to unity. However, the ratio in the plasma increased with time.     

奥芬达唑和阿苯达唑对猪囊尾蚴作用形态学比较观察

观察了奥芬达唑和阿苯达唑对猪体内及体外培养的不同发育阶段囊尾蚴作用的形态学效果.结果表明奥芬达唑具有显著的疗效,优于阿苯达唑,且对未成熟期猪囊尾蚴的杀灭作用优于成熟期.提示奥芬达唑可能成为抗未成熟期猪囊尾蚴及治疗脑囊虫病的有效药物.     

The disposition kinetics of albendazole following the administration of single and divided doses to cattle and buffalo

Concentrations of albendazole sulphoxide and its sulphone metabolite in plasma in cattle and buffalo were measured by high-performance liquid chromatography after single and divided intraruminal administration of albendazole at the recommended nematocidal and fasciolicidal dose rates of 7.5 and 15.0 mg/kg body weight, respectively. No significant differences in the plasma concentrations of the metabolites or their pharmacokinetic parameters were observed between cattle or buffalo at either dose rate. Pharmacokinetic analysis and the disposition curve of the metabolites indicated increased uptake of the drug in both cattle and buffalo when the same total amount of the drug was given in divided doses compared to a single dose (p<0.05). The divided dose schedules of administration could possibly be exploited to extend the life of the available benzimidazole anthelmintics.