伊维菌素药动学研究进展

综述了伊维菌素在动物体内的吸收、分布、代谢、排泄过程以及其药代动力学研究进展,以期为伊维菌素的临床用药和新兽药开发提供依据。     

伊维菌素制剂在动物寄生虫病防治中的研究进展

兽用伊维菌素是一种广谱抗寄生虫药,因具有高效、广谱、毒副作用小的特点而被广泛应用于动物体内外寄生虫病的临床治疗和防治中。文章综述了伊维菌素的理化特性、药理作用、剂型发展、临床应用、安全性和耐药性,并对其应用前景进行了展望,以期为今后伊维菌素在动物医学中的应用提供参考。     

驱虫抗生素莫西菌素的研究应用进展

莫西菌素(Moxidectin)一种目前广泛用于兽医临床的广谱、高效、新型大环内酯类驱虫抗生素，是美贝霉素(Mibemycin)家族中的一员。由于其独特的理化性质，在国外，莫西菌素已被广泛应用于治疗奶牛、猪等动物体内外寄生虫病，有取代伊维菌素的趋势。文章介绍了莫西菌素的理化性质、常用剂型，综述了药动学、药效学、耐药性、毒理学研究进展，为临床应用提供参考。     

浅析犬伊维菌素中毒机理及解救措施

伊维菌素是一类半合成大环内酯类多组分广谱抗寄生虫药,对动物体内线虫及疥螨、蜱、血虱等体外寄生虫都具有良好的驱杀效果。由于伊维菌素具有用药剂量小、抗虫效果好的特点,随着城镇宠物犬和农户厂矿看护犬养殖规模的扩大,犬寄生虫病感染愈来愈引起人们的重视。伊维菌素作为防治犬体内外寄生虫病的首选药物,在兽医临床上得到了广泛应用。但不合理地使用本品,导致犬发生依维菌素中毒的报道时有出现。本文通过浅析伊维菌素中毒的机理及解救措施,以此引起广大兽医人员在使用伊维菌素时的高度重视。     

浅析犬伊维菌素中毒机理及解救措施

伊维菌素是一类半合成大环内酯类多组分广谱抗寄生虫药,对动物体内线虫及疥螨、蜱、血虱等体外寄生虫都具有良好的驱杀效果。由于伊维菌素具有用药剂量小、抗虫效果好的特点,随着城镇宠物犬和农户厂矿看护犬养殖规模的扩大,犬寄生虫病感染愈来愈     

莫西菌素在养殖业中的应用与研究

正莫西菌素(Moxidectin)是一种新型抗寄生虫药,是由链霉菌发酵产生、半合成、成分单一的大环内酯类药物,是奈马菌素(Nemadectin)的衍生物,分子式为C37H53NO8,分子量为639.83,属于第3代阿维菌素类药物。莫西菌素与其他大环内酯类药的不同之处在于它是单一成分,有着更高的驱虫活性、长效和安全等特性。1理化性质及作用机理莫西菌素与其他同类药相比,有更高的脂溶性,水溶性也高于伊维菌素。因此,莫西菌素能与多种赋型剂组合制成各类制剂,有着不同的给药方式和药代动力学特性,安全性也比伊维菌素好。     

伊维菌素在西藏家畜寄生虫病治疗中的应用前景与展望

笔者通过查阅国内外伊维菌素新制剂的研究与应用报道,对不同剂型伊维菌素的药物疗效、药物安全性以及在西藏家畜寄生虫病防治中的困难和应用前景进行了详细阐述,最后对伊维菌素新制剂在西藏的推广与应用进行了展望,旨在希望伊维菌素新制剂能够在西藏家畜寄生虫病防治中能发挥更好的作用。     

阿维菌素和伊维菌素在牛、羊的应用

由于我国幅员辽阔，各地生态环境差异很大，很难制定出一种通用的驱虫方案；因此各地的用药方案都应在寄生虫病专家或兽医的指导下制定。阿维菌素和伊维菌素用于防治牛、羊寄生线虫和常见的外寄生虫有其独到之处。经过临床筛选后，我们认为阿维菌素对线虫的驱除作用最好。阿维菌素和伊维菌素是通过口服给药或皮下注射的方法驱除外寄生虫。因此可在任何时间。任何驱虫方案中应用。下面介绍一些用药方法。     

新一代驱虫抗生素—莫西菌素

莫西菌素同伊维菌素一样 ,是一种目前广泛用于兽医临床的广谱、高效、新型大环内酯类驱虫抗生素 ,是美贝霉素家族中的一员。由于其独特的理化性质 ,在国外 ,已被广泛用于治疗奶牛、猪等动物体内外寄生虫病。文章对莫西菌素的理化特性、作用机制、药动学、制剂、药效、耐药性、毒性、残留等进行了较详细地综述 ,同时也介绍了减少耐药性产生的一些方法 ,为该药能在国内应用提供第一手资料 ,以求为兽医临床用药提供参考     

家畜伊维菌素中毒的研究

作者综述了伊维菌素的杀虫及中毒机理,临床应用的安全性及犬、猫、羊、兔、牛的中毒剂量、临床症状、病理变化、预防、治疗措施,并说明了阿维菌素、伊维菌素和多拉菌素的应用。认为家畜中毒的原因是超量使用该药物;除敏感犬种外,伊维菌素是当前防治畜禽寄生虫病的最佳药物之一,同时指出对发生中毒和过敏的动物,早期发现,治疗得当,则治愈率高。     

Pharmacokinetics of a novel closantel/ivermectin injection in cattle

Two studies are described on the pharmacokinetics of a combination anthelmintic consisting of ivermectin and closantel for use in cattle. In the first, the pharmacokinetics of both active drugs in the combination were compared with the formulation with either ivermectin or closantel removed. No differences in the pharmacokinetics were observed, indicating that neither the absorption nor distribution of ivermectin or closantel in the combination were influenced by the presence of the other. In the second study the pharmacokinetics of ivermectin and closantel in the combination product were compared with control formulations of each. No difference was found between the closantel formulations. With ivermectin it was noted that absorption and excretion were more rapid and Cmax higher in the combination, although the AUC of both formulations were not significantly different.     

Ketoconazole increases the plasma levels of ivermectin in sheep

The parasiticide ivermectin and the antifungal drug ketoconazole are drugs that interact with P-glycoprotein. We have tested the ability of ketoconazole at a clinical dose to modify the pharmacokinetics of ivermectin in sheep. Lacaune lambs were administered with a single oral dose of ivermectin alone at 0.2mg/kg (n=5) or in combination with a daily oral dose of ketoconazole (10mg/kg) given for 3 days before and 2 days after the ivermectin (n=5). The plasma kinetics of ivermectin and its metabolite were followed over 15 days by HPLC analysis. Co-administration of ketoconazole induced higher plasma concentrations of ivermectin, leading to a substantial increase in the overall exposure of the animals to the drug. Ketoconazole did not reduce the production of the main ivermectin metabolite but it may rather act by inhibiting P-glycoprotein, and thus increasing the absorption of ivermectin. The use of a P-gp reversing agent such as ketoconazole could be useful tool to optimize antiparasitic therapy in the face of the worldwide development of anthelmintic resistance.     

Investigation of nutriactive phytochemical – gamma‐oryzanol in experimental animal models

Gamma‐oryzanol (GO) is an abundant dietary antioxidant that is considered to have beneficial effects in cardiovascular disease, cancer and diabetes. Other potential properties of GO include inhibition of gastric acid secretion and decreased post‐exercise muscle fatigue. GO is a unique mixture of triterpene alcohol and sterol ferulates present in rice bran oil, a byproduct of rice processing. GO has been studied by many researchers over the last three decades. In particular, the utility of GO supplementation has been documented in numerous animal models. A large variety of species was examined, and various experimental methodologies and targets were applied. The aim of this study was to summarize the body of research on GO supplementation in animals and to examine possible mechanisms of GO action. Furthermore, while the safety of GO supplementation in animals has been well documented, studies demonstrating pharmacokinetics, pharmacodynamics and efficiency are less clear. The observed differences in these findings are also discussed.     

Therapeutic implications of the MDR-1 gene

Drug transporters significantly influence drug pharmacokinetics and pharmacodynamics. P-glycoprotein (P-gp), the product of the MDR1 (ABCB1) gene, is among the most well-characterized drug transporters, particularly in veterinary medicine. A number of clinically relevant, structurally and functionally unrelated drugs are substrates for P-gp. P-gp is expressed by a variety of normal tissues including the intestines, renal tubular cells, brain capillary endothelial cells, biliary canalicular cells, and others, where it functions to actively extrude substrate drugs. In this capacity, P-gp limits oral absorption and central nervous system entry of many substrate drugs. A number of MDR1 polymorphisms have been described in human patients, some of which result in altered drug pharmacokinetics and susceptibility to diseases such as Parkinson's disease, inflammatory bowel disease, refractory seizures, and others. An MDR1 polymorphism in herding breed dogs, including collies and Australian shepherds, has been demonstrated to be the cause of ivermectin sensitivity in these breeds. Recent evidence suggests that this polymorphism, a 4-bp deletion mutation, results in increased susceptibility to the toxicity of several drugs in addition to ivermectin. Furthermore, data in rodent models suggest that P-gp may play an important role in regulating the hypothalamic-pituitary-adrenal axis.     

Cetirizine in horses: pharmacokinetics and effect of ivermectin pretreatment

The pharmacokinetics of the histamine H(1)-antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. After oral administration of cetirizine at 0.2 mg/kg bw, the mean terminal half-life was 3.4 h (range 2.9-3.7 h) and the maximal plasma concentration 132 ng/mL (101-196 ng/mL). The time to reach maximal plasma concentration was 0.7 h (0.5-0.8 h). Ivermectin (0.2 mg/kg bw) given orally 1.5 h before cetirizine did not affect its pharmacokinetics. However, ivermectin pretreatment 12 h before cetirizine increased the area under the plasma concentration-time curve by 60%. The maximal plasma concentration, terminal half-life and mean residence time also increased significantly following the 12 h pretreatment. Ivermectin is an inhibitor of P-glycoprotein, which is a major drug efflux transporter in cellular membranes at various sites. The elevated plasma levels of cetirizine following the pretreatment with ivermectin may mainly be due to decreased renal secretion, related to inhibition of the P-glycoprotein in the proximal tubular cells of the kidney. The pharmacokinetic properties of cetirizine have characteristics which are suitable for an antihistamine, and this substance may be a useful drug in horses.     

Efficacy and pharmacokinetics of febantel and ivermectin in red deer (Cervus elaphus)

A trial was conducted to determine the efficacy and pharmacokinetics of fehantel and ivermectin in six month-old red deer calves (C. eluphus). Five calves received febantel by mouth at 7.5 mg/kg, five received a subcutaneous injection of ivermectin at 200 microg/kg and five were controls. All calves were killed seven days later and total lung and gastrointestinal worm counts carried out. Febantel was 85 and 99.8% efficient in removing immature and mature Dictyocaulus viviparus, respectively, and ivermectin was 100% efficient in both cases. There was no gastro-intestinal nematodes in any of the treated calves, compared to an average of 619 in the control calves. The metabolism of febantel resulted in plasma levels of fenbendazole, oxfendazole and sulphone for which the common curves fitted by compartmental model peaked at values (standard errors)-of 0.46 (0.03), 0.41 (0.02) and 1.73 (0.07) mg/l after approximately five, nine, and thirteen hours and were undetectable at 30,72 and 120 hours respectively. There was considerable variation among animals in response to ivermectin. The fitted common curve had a peak plasma level of 15.8 (0.08) microg/l at 20 hours after injection, which had dropped to 7.9 (1.1) microg/l seven days after injection. It was estimated that after 15 days plasma levels of ivermectin would not be detectable. It is concluded that the injectable form of ivermectin tested is a highly efficient anthelmintic in deer, and that plasma levels persist for over a week after subcutaneous injection. Fehantel is very efficient against mature D. viviparus in deer, but its reduced efficiency against immature D. viviparus may relate to the deer;s ability to metabolise and excrete benzimidazoles more quickly than sheep and cattle.     

Enhancement of moxidectin bioavailability in lamb by a natural flavonoid: quercetin

Moxidectin is an antiparasitic drug widely used in cattle, sheep and companion animals. Due to the involvement of P-glycoprotein (P-gp) and cytochrome P450 3A in the metabolism of moxidectin, we studied the influence of various P-gp interfering agents (ivermectin, quercetin and ketoconazole) on the metabolism of 14C moxidectin in cultured rat hepatocytes over 72 h. This in vitro study allowed selection of compounds which are able to increase the moxidectin bioavailability in lambs. From this, the modulation of moxidectin pharmacokinetics in plasma of lambs was studied after co-administration of 0.2 mg kg(-1) moxidectin (subcutaneously (SC)) and 0.2 mg kg(-1) ivermectin (SC), or 10 mg kg(-1) quercetin (SC), or 10 mg kg(-1) ketoconazole (orally). Ivermectin and quercetin increased significantly the quantity of 14C moxidectin in the rat hepatocytes. Ketoconazole co-administration led to a higher concentration of moxidectin in the rat hepatocytes. In vivo, only quercetin was able to modify the pharmacokinetics of moxidectin in plasma of lambs by increasing significantly the area under the plasma concentration-time curve. This study allowed the use of a natural agent, quercetin, to improve the bioavailability of moxidectin.     

Impact of a sustained-release ivermectin bolus on weight gain in breeding age Holstein heifers under commercial pasture conditions in southern Québec.

This field trial was designed to test the effect of treatment with a sustained-release ivermectin bolus on average daily and total weight gain in breeding age Holstein heifers under commercial pasture conditions in southern Quebec. One hundred and twelve heifers from 12 herds were randomly assigned at turnout either to treatment with a commercially-available ivermectin bolus or to remain as untreated controls. Ninety-six heifers, 49 treated animals and 47 controls, completed the trial. Animals were weighed at turnout, midseason, and at the end of the grazing season. Fecal samples were collected at each of these times and nematode eggs counted. Nematode egg excretion was relatively low throughout the pasture season, which was abnormally warm and dry until midsummer. Over the entire pasture season, average daily weight gain was higher in treated than in control animals (difference = 0.08 kg/day, P = 0.010). Total weight gain was also higher in treated animals than in control animals (difference = 12.82 kg, P = 0.013). The results of this study suggest that preventive treatment of breeding age, grazing dairy heifers with a sustained-release ivermectin bolus provides a significant weight gain advantage, in situations with moderate utilization of moderately contaminated pastures.     

Efficacy and safety of clorsulon used concurrently with ivermectin for control of Fasciola hepatica in Florida beef cattle

The safety and anthelmintic efficacy of clorsulon (7 mg/kg of body weight, orally) given concurrently with ivermectin (0.2 mg/kg, subcutaneously) for control of Fasciola hepatica were evaluated in 75 crossbred beef cattle. Twenty-three control animals were given only ivermectin. Fluke egg counts were significantly lower (P less than 0.0001) in clorsulon-treated animals by day 14 after treatment than before treatment (base line) and were significantly lower (P less than 0.005) after treatment in clorsulon-treated animals than in controls. There was no significant change in fluke egg counts of controls after treatment. The efficacy of clorsulon in reducing F hepatica egg counts was 99%. Clorsulon showed poor efficacy against paramphistomes. Adverse reactions were not observed.