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Olsen L.R.,Copenhagen University | Gabel-Jensen C.,Copenhagen University | Nielsen P.A.,EntomoPharm | Hansen S.H.,Copenhagen University | Badolo L.,Lundbeck
Drug Metabolism and Disposition | Year: 2014

Insects have been proposed as a new tool in early drug development. It was recently demonstrated that locusts have an efflux transporter localized in the blood-brain barrier (BBB) that is functionally similar to the mammalian P-glycoprotein efflux transporter. Two insect BBB models have been put forward, an ex vivo model and an in vivo model. To use the in vivo model it is necessary to fully characterize the locust as an entire organism with regards to metabolic pathways and excretion rate. In the present study, we have characterized the locust metabolism of terfenadine, a compound that in humans is specific to the cytochrome P450 enzyme 3A4. Using high-resolution mass spectrometry coupled to ultra-high-performance liquid chromatography, we have detected metabolites identical to human metabolites of terfenadine. The formation of human metabolites in locusts was inhibited by ketoconazole, a mammalian CYP3A4 inhibitor, suggesting that the enzyme responsible for the human metabolite formation in locusts is functionally similar to human CYP3A4. Besides the human metabolites of terfenadine, additional metabolites were formed in locusts. These were tentatively identified as phosphate and glucose conjugates. In conclusion, not only may locusts be a model useful for determining BBB permeation, but possibly insects could be used in metabolism investigation. However, extensive characterization of the insect model is necessary to determine its applicability. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics. Source


Trademark
EntomoPharm | Date: 2012-05-15

Pharmaceutical and Veterinarian preparations for use in blood brain barrier screening to determine the biomembrane permeability for the treatment of depression, schizophrenia, chronic pain, epilepsy, cancer, spinal cord trauma, neurological diseases, Huntingtons disease, blood-brain barrier related malfunctions, obesity, fungal infections, A.L.S., multiple sclerosis, neuro-AIDS, progressive multifocal leukoenceplalopathy, autism, lysosomal storage disorders, fragile X syndrome, inherited mental retardation, inherited ataxias, prion disease, meningitis, neuromyelitis optica, late-stage neurological trypanosomiasis, parasitic diseases, De Vivo disease, rabies, encephalitis, locked-in syndrome and bacterial infections. Scientific, technological and industrial services, namely, scientific research, analysis, testing in the field of pharmaceutical and drug development; Industrial analysis and research services for human and veterinarian pharmaceuticals. Agriculture advice; Forestry services, namely, vermin and pest control services; forest habitat restoration.


There is provided an ex-vivo insect screening model to accurately determine blood-brain barrier penetration of different nanoparticles in order to improve the compound screening procedures/processes in the early drug discovery process. This object offers many advantages relative to prior technologies since insect models are more reliable tools for the decision-making process than the existing in vitro models, and will speed up the drug screening process and reduce the late phase attrition rate. Moreover, it will reduce the number of mammals sacrificed during the drug discovery phase.


There is provided an ex-vivo insect screening model to accurately determine blood-brain barrier penetration of different chemical compounds in order to improve the compound screening procedures/processes in the early drug discovery process. This object offers many advantages relative to prior technologies since insect models are more reliable tools for the decision-making process than the existing in vitro models, and will speed up the drug screening process and reduce the late phase attrition rate. Moreover, it will reduce the number of mammals sacrificed during the drug discovery phase.


Patent
EntomoPharm | Date: 2010-08-10

There is provided a new methodology for initial assessment of compound PK. The invention is generally particular useful for efficient screening of and assessment of PK profiles of newly synthesized compounds in the early phase of drug discovery.

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