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Safety, pharmacokinetics, and pharmacodynamics of TV-1380, a novel mutated butyrylcholinesterase treatment for cocaine addiction, after single and multiple intramuscular injections in healthy subjects.
J Clin Pharmacol ; 55(5): 573-83, 2015 May.
Article em En | MEDLINE | ID: mdl-25524052
Human plasma butyrylcholinesterase (BChE) contributes to cocaine metabolism and has been considered for use in treating cocaine addiction and cocaine overdose. TV-1380 is a recombinant protein composed of the mature form of human serum albumin fused at its amino terminus to the carboxy-terminus of a truncated and mutated BChE. In preclinical studies, TV-1380 has been shown to rapidly eliminate cocaine in the plasma thus forestalling entry of cocaine into the brain and heart. Two randomized, blinded phase I studies were conducted to evaluate the safety, pharmacokinetics, and pharmacodynamics of TV-1380, following single and multiple administration in healthy subjects. TV-1380 was found to be safe and well tolerated with a long half-life (43-77 hours) and showed a dose-proportional increase in systemic exposure. Consistent with preclinical results, the ex vivo cocaine hydrolysis, TV-1380 activity clearly increased upon treatment in a dose-dependent manner. In addition, there was a direct relationship between ex vivo cocaine hydrolysis (kel ) and TV-1380 serum concentrations. There was no evidence that TV-1380 affected heart rate, the uncorrected QT interval, or the heart-rate-corrected QTcF interval. TV-1380, therefore, offers a safe once-weekly therapy to increase cocaine hydrolysis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Recombinantes de Fusão / Butirilcolinesterase / Transtornos Relacionados ao Uso de Cocaína / Albuminas Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Female / Humans / Male Idioma: En Revista: J Clin Pharmacol Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Israel

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Recombinantes de Fusão / Butirilcolinesterase / Transtornos Relacionados ao Uso de Cocaína / Albuminas Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Female / Humans / Male Idioma: En Revista: J Clin Pharmacol Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Israel