Suri A, Estes K S, Geisslinger G, Derendorf H
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, USA.
Int J Clin Pharmacol Ther. 1997 Aug;35(8):307-23.
A major goal of current pain research is to develop scientifically-based guidelines to optimize selection of analgesic drug doses and control pain. Numerous clinical studies have shown that the drug dose required to effectively alleviate pain is often highly variable, both between patients and between pain episodes in individual patients. This high variability makes it difficult to predict appropriate dosing regimens that will adequately control pain in the individual patient. The result is a "trial and error" approach to analgesic therapy. Experimental tools that measure analgesic response and drug disposition after administration of analgesics can be used to better predict the therapeutic effects of analgesics in individual patients. The approach defines factors that contribute to variability in therapeutic response. Pharmacokinetic-pharmacodynamic (PK/PD) modeling involves analysis of drug disposition data and drug efficacy data. Modeling depends on sensitive and reliable methods to quantify both pain and plasma (or other body fluid) levels of analgesic agents. Two major approaches have been used to quantify pain. The first utilizes subjective reports from patients, while the second employs physiological correlates of pain, such as evoked potentials. Results from PK/PD analysis that successfully identify a relationship between drug dose, drug concentration, and effect can be used to predict the effects of drug dose on analgesic effect in individuals. The ultimate goal is to provide patients with better pain relief by understanding variables that affect the analgesic concentration/effect relationship. This review examines the available pharmacokinetic-pharmacodynamic (PK/PD) data for selected opioid and nonopioid analgesics. Even though most analgesics are used clinically in multiple doses, the majority of PK/PD studies conducted to date evaluate single dose effects. Further studies with multiple doses are required to evaluate the validity of PK/PD relationships defined from single dose studies.
当前疼痛研究的一个主要目标是制定基于科学的指南，以优化镇痛药剂量的选择并控制疼痛。大量临床研究表明，有效缓解疼痛所需的药物剂量在患者之间以及个体患者的不同疼痛发作之间往往差异很大。这种高度变异性使得难以预测能充分控制个体患者疼痛的合适给药方案。结果导致镇痛药治疗采用“试错”方法。在给予镇痛药后测量镇痛反应和药物处置的实验工具可用于更好地预测镇痛药在个体患者中的治疗效果。该方法确定了导致治疗反应变异性的因素。药代动力学 - 药效学（PK/PD）建模涉及对药物处置数据和药物疗效数据的分析。建模依赖于敏感且可靠的方法来量化镇痛药的疼痛和血浆（或其他体液）水平。已使用两种主要方法来量化疼痛。第一种方法利用患者的主观报告，而第二种方法采用疼痛的生理相关指标，如诱发电位。成功识别药物剂量、药物浓度和效应之间关系的PK/PD分析结果可用于预测药物剂量对个体镇痛效果的影响。最终目标是通过了解影响镇痛浓度/效应关系的变量，为患者提供更好的疼痛缓解。本综述考察了选定的阿片类和非阿片类镇痛药的现有药代动力学 - 药效学（PK/PD）数据。尽管大多数镇痛药在临床上采用多剂量使用，但迄今为止进行的大多数PK/PD研究评估的是单剂量效应。需要进一步进行多剂量研究，以评估从单剂量研究中确定的PK/PD关系的有效性。
