Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Expert Rev Clin Pharmacol. 2008 Mar;1(2):277-90. doi: 10.1586/17512433.1.2.277.
The pharmacokinetic approach to treatment targets the drug molecules themselves, aiming to reduce their concentration at the site of action, thereby reducing or preventing any pharmacodynamic effect. This approach might be useful in the treatment of acute drug toxicity/overdose and in the long-term treatment of addiction. Early clinical trials with anticocaine and antinicotine vaccines have shown reduced drug use and good tolerability. Also showing promise in animal studies are monoclonal antibodies against cocaine, methamphetamine and phencyclidine, as well as the enhancment of cocaine metabolism with genetic variants of human butyrylcholinesterase, using a bacterial esterase or catalytic monoclonal antibodies. Pharmacokinetic treatments offer potential advantages in terms of patient compliance, absence of medication interactions and benefit for patients who cannot take standard medications.
治疗的药代动力学方法针对的是药物分子本身,旨在降低其在作用部位的浓度,从而减少或防止任何药效学作用。这种方法在治疗急性药物毒性/中毒和长期治疗成瘾方面可能有用。抗可卡因和抗尼古丁疫苗的早期临床试验显示,药物使用减少,且耐受性良好。在动物研究中也有希望的是针对可卡因、甲基苯丙胺和苯环利定的单克隆抗体,以及利用人丁酰胆碱酯酶的遗传变异体增强可卡因代谢的方法,使用细菌酯酶或催化单克隆抗体。在患者依从性、不存在药物相互作用以及对不能服用标准药物的患者有益方面,药代动力学治疗提供了潜在的优势。