Patat A A
Wyeth-Lederle, Division Wyeth-Ayerst Research, Clinical Pharmacology, Paris-La Défense, France.
Dialogues Clin Neurosci. 2000 Sep;2(3):203-12. doi: 10.31887/DCNS.2000.2.3/apatat.
First human administration of a new chemical entity (NCE) constitutes a critical step in drug development. The primary objective of such a study is the assessment of the shortterm safety and tolerability of single and multiple doses of the NCE in healthy volunteers. Secondary objectives are to obtain preliminary data on the pharmacokinetics and pharmacodynamics using surrogate or biornarkers of the beneficial as well as the adverse effects of the drug. Interpretation of safety data should be cautious and mainly based on comparisons with placebo. A special focus should be made on the assessment of adverse events, liver enzymes, and cardiac repolarization. Well-designed, first-time-to-man studies should determine the safety of the NCE in humans and predict the dose range that may be used to safely and accurately conduct further clinical trials in the target patient population based on safety data (maximum tolerated dose), pharmacodynamics (minimum active dose, duration of action, and dosage regimen), and pharmacokinetics (dosage regimen).
新化学实体（NCE）首次在人体给药是药物研发中的关键一步。此类研究的主要目的是评估单剂量和多剂量NCE在健康志愿者中的短期安全性和耐受性。次要目的是使用药物有益和不良反应的替代指标或生物标志物获取有关药代动力学和药效学的初步数据。对安全性数据的解释应谨慎，且主要基于与安慰剂的比较。应特别关注不良事件、肝酶和心脏复极化的评估。精心设计的首次人体研究应确定NCE在人体中的安全性，并根据安全性数据（最大耐受剂量）、药效学（最小有效剂量、作用持续时间和给药方案）和药代动力学（给药方案）预测可用于在目标患者群体中安全、准确地开展进一步临床试验的剂量范围。
