Pharmacokinetic Strategies for Treatment of Drug Overdose and Addiction

Abstract

The pharmacokinetic treatment strategy targets the drug molecule itself, aiming to reduce drug concentration at the site of action, thereby minimizing any pharmacodynamic effect. This approach might be useful in the treatment of acute drug toxicity/overdose and in the long-term treatment of addiction. Phase IIa controlled clinical trials with anticocaine and antinicotine vaccines have shown good tolerability and some efficacy, but Phase IIb and III trials have been disappointing because of the failure to generate adequate antibody titers in most participants. Monoclonal antibodies against cocaine, methamphetamine and phencyclidine have shown promise in animal studies, as has enhancing cocaine metabolism with genetic variants of human butyrylcholinesterase, with a bacterial esterase, and with catalytic monoclonal antibodies. Pharmacokinetic treatments offer potential advantages in terms of patient adherence, absence of medication interactions and benefit for patients who cannot take standard medications.

Agonist Medications for the Treatment of Cocaine Use Disorder

“…The m-opioid receptor antagonist naltrexone, which is approved for treatment of opioid-use disorders, is one example of an antagonist medication that can have high therapeutic efficacy and safety under appropriate conditions. However, compliance has been a significant obstacle to the use of naltrexone (Comer et al, 2007) and antagonist approaches have not yet succeeded as viable pharmacotherapies for cocaine-use disorder (Gorelick, 2012;Grabowski et al, 2000;Haney et al, 2001).…”

Protein Engineering: A New Frontier for Biological Therapeutics

“…In particular, enzymatic antidotes are targeted for the treatment of overdoses of abused drugs and for addiction control [41]. Most noteworthy has been the development of hydrolases for the neutralization of cocaine (Fig.…”

Hapten Optimization for Cocaine Vaccine with Improved Cocaine Recognition

“…Conventional pharmacological treatment strategies that aim to target the drug sites of action using different small molecule agonists and antagonists have not produced any effective treatment options for cocaine addicts thus far (2, 3). In response to these limitations, immunotherapy has been actively pursued as a different treatment strategy that targets the cocaine molecule directly, aiming to keep the target drug below its minimum effective concentration (MEC) at its sites of action (3).…”

“…Conventional pharmacological treatment strategies that aim to target the drug sites of action using different small molecule agonists and antagonists have not produced any effective treatment options for cocaine addicts thus far (2, 3). In response to these limitations, immunotherapy has been actively pursued as a different treatment strategy that targets the cocaine molecule directly, aiming to keep the target drug below its minimum effective concentration (MEC) at its sites of action (3). Since the site of pharmacological effect against cocaine is in the pleasure circuit inside the brain, it was hypothesized that antibodies against cocaine would sequester much of the cocaine in the peripheral circulation before it cross the blood brain barrier (4).…”