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Diclazuril: Introduction;Administered;Mechanism of action

Dec 7，2023

Introduction of Diclazuril

Diclazuril is a less toxic, orally administered triazine antiprotozoal. It is widely used in veterinary medicine as a feed additive and veterinary drug. It is registered for oral use in broilers and lambs. Its use in cats (one dose of 25 mg/kg BW) is off-label only. It may be used clinically for the treatment of bovine protozoa. It is also used for the treatment of equine protozoan spinal cord encephalitis (EPM) caused by neuronal sarcocysts.

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Diclazuril Administered

This study reports the bioavailability, pharmacokinetics and metabolism of diclazuril sodium salt in cattle after direct application to the oral mucosa by suspending diclazuril sodium salt in water. Absorption of the diclazuril sodium salt formulation was rapid and reliable when applied to the oral mucosa compared to diclazuril itself. Plasma concentrations of diclazuril peaked approximately 8 hours after oral mucosal administration of diclazuril sodium salt. In contrast, oral administration of diclazuril itself results in a different delayed absorption. The average bioavailability of diclazuril as a pure powder compared to diclazuril sodium salt was 42.5%, suggesting that the bioavailability of diclazuril as a sodium salt is approximately 2.5-fold higher in cattle compared to diclazuril as a pure compound.

Mechanism of action

Although the mode of action of dilazuril is unknown, its effect on the asexual or sexual stages of coccidia can prevent the excretion of oocysts, which can lead to disruption of the parasite's life cycle.

Cyclin-dependent kinases (CDK) are prominent target proteins in apicomplexan parasites. In this study, a diclazuril anticoccidiosis animal model was established, transcription translation levels CDK-related kinase 2 Eimeria tenella (EtCRK2) were detected. mRNA protein expression levels EtCRK2 decreased in infected/diclazuril group compared with those in infected/control group. In addition, immunofluorescence analysis showed that EtCRK2 was localised in cytoplasm merozoites. The fluorescence intensity EtCRK2 in infected/diclazuril group was significantly weaker than that in infected/control group. The anticoccidial drug diclazuril against E.tenella affects expression pattern EtCRK2 molecule, EtCRK2 is a potential target for new drug development.

References:

[1] LEVENT DIRIKOLU Thomas T Andreas Fritz Lehner. Plasma concentrations of diclazuril following oral administration of diclazuril and diclazuril sodium salt to cattle[J]. Journal of veterinary pharmacology and therapeutics, 2022, 45 4: 392-401. DOI:10.1111/jvp.13062.

[2] BIAN-HUA ZHOU . Diclazuril-induced expression of CDK-related kinase 2 in the second-generation merozoites of Eimeria tenella[J]. Molecular and biochemical parasitology, 2023, 255: Article 111575. DOI:10.1016/j.molbiopara.2023.111575.

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