Pharmacokinetic strategies for treatment of drug overdose and addiction.
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.
Chemistry & Drug Metabolism Section Intramural Research Program, National Institute on Drug Abuse, NIH, 251 Bayview Boulevard, Baltimore, MD 21224, USA. dgorelic@intra.nida.nih.gov
David A
DA
Gorelick
D017322:Clinical Trials, Phase II as Topic; D062787:Drug Overdose / Q000188:drug therapy*; D006801:Humans; D010599:Pharmacokinetics; D019966:Substance-Related Disorders / Q000188:drug therapy*