Merck
  • Home
  • Search Results
  • The effects of a humanized recombinant anti-cocaine monoclonal antibody on the disposition of cocaethylene in mice.

The effects of a humanized recombinant anti-cocaine monoclonal antibody on the disposition of cocaethylene in mice.

International immunopharmacology (2014-12-03)
Hanna N Wetzel, Michael R Tabet, William J Ball, Andrew B Norman
ABSTRACT

The chimeric human/mouse anti-cocaine monoclonal antibody (mAb) 2E2 and its further humanized variant h2E2 have been reported to sequester a significant portion of cocaine in plasma and decrease cocaine concentrations in the brain in mice and rats. However, many cocaine users co-abuse alcohol, leading to the formation of the centrally active metabolite cocaethylene. This potentially compromises the efficacy of a cocaine-specific immunotherapy. Because h2E2 has high affinity for cocaethylene as well as cocaine, the ability of h2E2 to prevent cocaethylene entry into the brain was investigated. Mice were infused with h2E2 (1.6 μmol/kg i.v.) or vehicle and after one hour were injected with cocaethylene fumarate (1.2 μmol/kg i.v.). At times from 45 s to 60 min, brain and plasma were collected and cocaethylene concentrations were measured using GC/MS. In control mice, a two-compartment pharmacokinetic model generated values for cocaethylene distribution and terminal elimination half-lives of 0.5 and 8.1 min respectively. Initial plasma cocaethylene concentrations increased 13-fold from controls in the presence of h2E2. In brain, h2E2 produced a 92% decrease in the area under the time-concentration curve for cocaethylene. The pharmacokinetics of h2E2 was also characterized in detail. A three-compartment model resolved an initial distribution half-life of 4.4 min and a second distribution half-life of 4.2 h, and a terminal elimination half-life of 7.8 days. The ability of h2E2 to protect the brain from both cocaine and cocaethylene predicts that the clinical efficacy of h2E2 will be retained in cocaine users who co-abuse alcohol.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Chlorotrimethylsilane, purified by redistillation, ≥99%
Sigma-Aldrich
Chlorotrimethylsilane, ≥98.0% (GC)
Sigma-Aldrich
Chlorotrimethylsilane, puriss., ≥99.0% (GC)
Sigma-Aldrich
Chlorotrimethylsilane, produced by Wacker Chemie AG, Burghausen, Germany, ≥99.0% (GC)
Sigma-Aldrich
Acetonitrile solution, contains 0.05 % (v/v) trifluoroacetic acid
Supelco
Chlorotrimethylsilane, for GC derivatization, LiChropur, ≥99.0% (GC)
Supelco
Cocaethylene solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Residual Solvent - Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Chlorotrimethylsilane solution, 1.0 M in THF
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
Supelco
Acetonitrile, analytical standard
Sigma-Aldrich
Acetonitrile, ACS reagent, ≥99.5%
Sigma-Aldrich
Acetonitrile, suitable for DNA synthesis, ≥99.9% (GC)
Sigma-Aldrich
Acetonitrile, biotech. grade, ≥99.93%
Sigma-Aldrich
Acetonitrile, ReagentPlus®, 99%
Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Acetonitrile, HPLC Plus, ≥99.9%
Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Acetonitrile, electronic grade, 99.999% trace metals basis
Sigma-Aldrich
Acetonitrile, for DNA synthesis
Sigma-Aldrich
Ultrapure Acetonitrile
USP
Residual Solvent Class 2 - Acetonitrile, United States Pharmacopeia (USP) Reference Standard
Supelco
Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material