Assessment of Pharmacokinetic and Pharmacodynamic Interactions Between Albumin-Fused Mutated Butyrylcholinesterase and Intravenously Administered Cocaine in Recreational Cocaine Users

Abstract

Administration of Albu-BChE at single doses of 50, 100, and 300 mg safely resulted in long-lasting decreases in cocaine exposure in recreational cocaine users.

Biologics to treat substance use disorders: Current status and new directions

“…9,18 Cocaine-degrading enzymes derived from human plasma butyrylcholinesterases (BChE) and bacterial cocaine esterases (CocE) have been tested for treatment of cocaine dependence and overdose (NCT01887366, and NCT01846681, Table 1). [148][149][150] These clinical studies showed no evidence of side effects, and provide proof of concept for enzyme-based SUD treatments. A detailed review of clinical studies of cocaine esterases can be found elsewhere.…”

Effects of a cocaine hydrolase engineered from human butyrylcholinesterase on metabolic profile of cocaine in rats

“…The first one of our designed CocHs, known as CocH1 (the A199S/S287G/A328W/Y332G mutant of human BChE) [10, 14], was fused with human serum albumin (HSA) to prolong the biological half-life [8], and the obtained HSA-fused CocH1 is also known as Albu-CocH, Albu-CocH1, AlbuBChE, or TV-1380 in literature [6–8, 15]. Clinical trials demonstrated that TV-1380 is safe and effective for use in animals and humans [6, 7], but its actual therapeutic value for cocaine addiction treatment is still limited by the moderate biological half-life (~8 hr in rats [8] or 43–77 hr in humans [6]). Generally speaking, the biological half-life of a therapeutic protein in humans is significantly longer than that in rats [8].…”

Reply to Curry and Coombs: Benzoic acid is formed predominantly from the benzoyl ester hydrolysis in the presence of cocaine hydrolase

“…However, under the experimental conditions described in our study (2), the NC pathway is actually negligible. As is well known, when a highly efficient cocaine-metabolic enzyme, such as CocH3 or CocH3-Fc(M3) (2), is available to considerably accelerate cocaine hydrolysis to EME + BA in the body, cocaine metabolism via the other pathways are significantly reduced (3)(4)(5). In fact, we tried to measure the concentrations of other metabolites (including EME, NC, BE, and ecgonine) in the blood samples collected in our study (2), and concluded that there were no detectable NC concentrations in the blood samples.…”