An albumin-butyrylcholinesterase for cocaine toxicity and addiction: Catalytic and pharmacokinetic properties

Yang Gao, David LaFleur, Rutul Shah, Qinghai Zhao, Mallika Singh, William Stephen Brimijoin

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Butyrylcholinesterase (BChE, EC 3.1.1.8) is important in human cocaine metabolism despite its limited ability to hydrolyze this drug. Efforts to improve the catalytic efficiency of this enzyme have led to a quadruple mutant cocaine hydrolase, "CocH", that in animal models of addiction appears promising for treatment of overdose and relapse. We incorporated the CocH mutations into a BChE-albumin fusion protein, "Albu-CocH", and evaluated the pharmacokinetics of the enzyme after i.v. injection in rats. As assessed from the time course of cocaine hydrolyzing activity in plasma, Albu-CocH redistributed into extracellular fluid (16% of estimated total body water) with a t1/2 of 0.66 h and it underwent elimination with a t1/2 of 8 h. These results indicate that the enzyme has ample stability for short-term applications and may be suitable for longer-term treatment as well. Present data also confirm the markedly enhanced power of Albu-CocH for cocaine hydrolysis and they support the view that Albu-CocH might prove valuable in treating phenomena associated with cocaine abuse.

Original languageEnglish (US)
Pages (from-to)83-87
Number of pages5
JournalChemico-Biological Interactions
Volume175
Issue number1-3
DOIs
StatePublished - Sep 25 2008

Fingerprint

Butyrylcholinesterase
Cocaine-Related Disorders
Pharmacokinetics
Cocaine
Toxicity
Albumins
Enzymes
Aptitude
Body Water
Cholinesterases
Extracellular Fluid
Hydrolases
Hydrolysis
Metabolism
Animal Models
Rats
Efficiency
Animals
Recurrence
Fusion reactions

Keywords

  • Albumin fusion protein
  • Butyrylcholinesterase
  • Cocaine hydrolase
  • Enzyme kinetics
  • Pharmacokinetics
  • Rats

ASJC Scopus subject areas

  • Toxicology

Cite this

An albumin-butyrylcholinesterase for cocaine toxicity and addiction : Catalytic and pharmacokinetic properties. / Gao, Yang; LaFleur, David; Shah, Rutul; Zhao, Qinghai; Singh, Mallika; Brimijoin, William Stephen.

In: Chemico-Biological Interactions, Vol. 175, No. 1-3, 25.09.2008, p. 83-87.

Research output: Contribution to journalArticle

Gao, Yang ; LaFleur, David ; Shah, Rutul ; Zhao, Qinghai ; Singh, Mallika ; Brimijoin, William Stephen. / An albumin-butyrylcholinesterase for cocaine toxicity and addiction : Catalytic and pharmacokinetic properties. In: Chemico-Biological Interactions. 2008 ; Vol. 175, No. 1-3. pp. 83-87.
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