Potentiation of triclabendazole action in vivo against a triclabendazole-resistant isolate of Fasciola hepatica following its co-administration with the metabolic inhibitor, ketoconazole

An in vivo study in the laboratory rat model has been carried out to monitor morphological changes in adult Fasciola hepatica over a 4-day period resulting from co-treatment with triclabendazole (TCBZ) and ketoconazole (KTZ), a cytochrome P450 inhibitor. Rats were infected with the triclabendazole-resistant Oberon isolate of F. hepatica, dosed orally with triclabendazole at a dosage of 10 mg/kg live weight and ketoconazole at a dosage of 10 mg/kg live weight. Flukes were recovered at 24, 48, 72 and 96 h post-treatment (p.t.) and changes to fluke ultrastructure were assessed using transmission electron microscopy (TEM). Results showed an increase in the severity of changes to the fluke ultrastructure with time p.t. Swelling of the basal infolds and the associated mucopolysaccharide masses became more severe with time. Golgi complexes, if present, were greatly reduced in size and number by 96 h p.t., and sub-tegumental flooding was seen from the 72 h time-period onwards. Some sloughing of the tegumental covering over the spines was observed at 96 h p.t. The results demonstrated that the Oberon isolate is more sensitive to TCBZ action in the presence of KTZ than to TCBZ alone, reinforcing the idea that altered drug metabolism is involved in the resistance mechanism. Moreover, they support the concept that TCBZ + inhibitor combinations (aimed at altering drug pharmacokinetics and potentiating the action of TCBZ) could be used in the treatment of TCBZ-R populations of F. hepatica.     

P‐Glycoprotein Mediated Drug Interactions in Animals and Humans with Cancer

Drug–drug interactions can cause unanticipated patient morbidity and mortality. The consequences of drug–drug interactions can be especially severe when anticancer drugs are involved because of their narrow therapeutic index. Veterinary clinicians have traditionally been taught that drug–drug interactions result from alterations in drug metabolism, renal excretion or protein binding. More recently, drug–drug interactions resulting from inhibition of P‐glycoprotein‐mediated drug transport have been identified in both human and veterinary patients. Many drugs commonly used in veterinary patients are capable of inhibiting P‐glycoprotein function and thereby causing an interaction that results in severe chemotherapeutic drug toxicity. The intent of this review is to describe the mechanism and clinical implications of drug–drug interactions involving P‐glycoprotein and anticancer drugs. Equipped with this information, veterinarians can prevent serious drug–drug interactions by selecting alternate drugs or adjusting the dose of interacting drugs.     

Brain abscess in a dog immunosuppressed using cyclosporin

This report describes a dog that developed brain abscesses following prolonged immunosuppression with cyclosporin. Bacteria within the abscess were most likely Nocardia, an organism well recognised in immunosuppressed humans, and probably reached the brain through haematogenous spread from a more long-standing abscess in the mediastinum. Bacterial brain abscesses developing in this manner are very rare in dogs and this case highlights the wider range of possible diagnoses that need to be considered in immunosuppressed patients and the care with which potent drugs such as cyclosporin should be used.     

高效液相色谱法同时测定兽药复方酮康唑软膏中的酮康唑和甲硝唑含量

建立了同时提取、测定兽药复方酮康唑软膏中酮康唑、甲硝唑含量的高效液相色谱(HPLC)法。采用C18色谱柱,甲醇-水为流动相,梯度洗脱,检测波长239nm。结果表明,酮康唑和甲硝唑2种成分线性关系良好(r > 0.999)。在3个不同浓度水平下酮康唑和甲硝唑平均加样回收率分别为 97.8% 和100.0%,溶液稳定性和方法重复性的RSD均小于1%。应用该方法测定3个不同厂家样品中2种组分的含量,结果符合要求。本方法简便,可靠,专属性强,重现性好,为该制剂的质量标准提高提供了研究基础。     

In vitro antifungal activities of Allium cepa, Allium sativum and ketoconazole against some pathogenic yeasts and dermatophytes

By using an agar dilution assay, the antifungal activity of aqueous extracts prepared from Allium cepa (onion; AOE) and Allium sativum (garlic; AGE) were evaluated against Malassezia furfur (25 strains), Candida albicans (18 strains), other Candida sp. (12 strains) as well as 35 strains of various dermatophyte species and compared with the activity of a known antifungal drug, ketoconazole (KTZ). All the AOE, AGE and KTZ were found to be able to inhibit growth of all fungi tested in a dose-dependent manner with maximum of 100% at defined concentrations. The results indicate that onion and garlic might be promising in treatment of fungal-associated diseases from important pathogenic genera Candida, Malassezia and the dermatophytes.