Chen M L, Lesko L, Williams R L
Office of Pharmaceutical Science, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20857, USA.
Clin Pharmacokinet. 2001;40(8):565-72. doi: 10.2165/00003088-200140080-00001.
Regulatory assessment of bioavailability and bioequivalence in the US frequently relies on measures of rate and extent of absorption. Rate of absorption is not only difficult to measure but also bears little clinical relevance. This paper proposes that measures of bioavailability and bioequivalence for drugs that achieve their therapeutic effects after entry into the systemic circulation are best expressed in terms of early [partial area under the concentration-time curve (AUC)], peak plasma or serum drug concentration and total AUC exposure for a plasma or serum concentration-time profile. With suitable documentation, these systemic exposure measures can be related to efficacy and tolerability outcomes. The early measure is recommended for an immediate release drug product where a better control of drug absorption is needed, for example to ensure rapid onset of a therapeutic effect or to avoid an adverse reaction from a fast input rate. The 3 systemic exposure measures for bioavailability and bioequivalence studies can provide critical links between product quality and clinical outcome and thereby reduce the current emphasis on rate of absorption.
在美国，生物利用度和生物等效性的监管评估常常依赖于吸收速率和程度的测量指标。吸收速率不仅难以测量，而且临床相关性不大。本文提出，对于进入体循环后发挥治疗作用的药物，其生物利用度和生物等效性的测量指标最好用早期[浓度-时间曲线下部分面积（AUC）]、血浆或血清药物峰浓度以及血浆或血清浓度-时间曲线的总AUC暴露量来表示。有了适当的文件记录，这些全身暴露量指标可与疗效和耐受性结果相关联。对于需要更好地控制药物吸收的速释制剂，例如为确保治疗效果迅速起效或避免因输入速率过快而产生不良反应的情况，建议采用早期测量指标。生物利用度和生物等效性研究的这3个全身暴露量指标可在产品质量和临床结果之间提供关键联系，从而减少目前对吸收速率的重视。
