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Petrov2018 - C-547 a 6-methyluracil derivative with long-lasting binding and rebinding on acetylcholinesterase

ABSTRACT: C-547, a candidate drug, is a potent slow-binding inhibitor of acetyl-cholinesterase, and the focus of this PK/PD model, which investigates the metabolism and clinical effect of C-547 when it is no longer detectable in the blood. Intended for treatment of myasthenia gravis, this drug and the accompanying model offers a possible treatment for further development of drugs offering neuroprotective effects.

SUBMITTER: Johannes Meyer

PROVIDER: MODEL1910240001 | BioModels | 2019-11-13

REPOSITORIES: BioModels

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C-547, a 6-methyluracil derivative with long-lasting binding and rebinding on acetylcholinesterase: Pharmacokinetic and pharmacodynamic studies.

Petrov Konstantin K Zueva Irina I Kovyazina Irina I Sedov Igor I Lushchekina Sofya S Kharlamova Alexandra A Lenina Oksana O Koshkin Sergei S Shtyrlin Yurii Y Nikolsky Evgeny E Masson Patrick P

Neuropharmacology 20171224

C-547, a potent slow-binding inhibitor of acetylcholinesterase (AChE) was intravenously administered to rat (0.05 mg/kg). Pharmacokinetic profiles were determined in blood and different organs: extensor digitorum longus muscle, heart, liver, lungs and kidneys as a function of time. Pharmacokinetics (PK) was studied using non-compartmental and compartmental analyses. A 3-compartment model describes PK in blood. Most of injected C-547 binds to albumin in the bloodstream. The steady-state volume of ...[more]

PMID: 29277489

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