统计数据表明，在1991年，药代动力学性质（PK）不佳是药物发现的主要阻碍。截至2000年，影响ADME（吸收、分布、代谢和排泄）的各项因素占据了相当大的比例，成为新的主要问题。其中，毒性问题占比更是增加了2倍多，足以引起药物研发者的重视(Nature Reviews Drug Discovery 3, 711-716(August 2004))。
HREG抑制活性
近些年来，大量药物由于引发急性心脏病被撤市。在所有案例中，多数病人的心电图显示出延长的QT间歇期，这一现象被认为是引发猝死的主要原因。HREG基因（KCNH2）编码的Kv11.1钾离子通道的阻滞是药物诱导的QT间歇期延长的成因。2005年，ICH出台了两项临床前评估心脏病风险的举措。其一，体外检测HERG钾离子通道电流是否被药物抑制；其二，体内检测用药后QT间歇期的变化。
诱变性
诱变性是指药物在基因水平诱导细胞或组织产生永久性可遗传的变化，包括单点突变、基因组或染色体的结构或数目的突变，通常会导致癌症。评价药物诱变性常用的检测方法有分为体外试验（Ames试验、小鼠淋巴瘤试验和微核试验等）和体内试验（检测啮齿类动物造血干细胞的微核和染色体突变等）。
药物-药物相互作用
许多药物相互作用的产生是由于药物A影响了药物B的代谢，发挥作用的主要是细胞色素P450氧化酶系（CYP450），根据作用的不同，可分为酶抑制和酶诱导。
肝毒性
药物诱导的肝毒性在急性肝损伤中占比超过50%，造成极高的发病率和致死率，是药物撤市的主要原因。因肝毒性撤市的药物有溴芬酸（bromfenac）、乙溴替丁（ebrotidine）、曲格列酮（troglitazone）等，其中有剧烈肝毒性的药物如利培酮（risperidone）、曲伐沙星（risperidone）和奈法唑酮（nefazodone）更是被冠以“黑箱（black box）”警告。
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