Detailed ADME (absorption, distribution, metabolism and excretion) evaluation is required in the preclinical stage of drug development. The preclinical ADME data may be extrapolated to humans and some predictions may be made with the application of proper pharmacokinetic and pharmacodynamic principles. Novel drugs with validated drug targets and favorable ADME properties are being sought by drug scientists, and oral administration is becoming a major delivery approach for many drugs due to its great safety, reduced cost, improved quality of life, and the potential for improved efficacy. The incorporation of herbal therapy into the main stream medical-care system has been encouraged by World Health Organization (WHO). Chinese herbal medicines may represent an important group of multi-component therapeutics suitable for the management of diseases with networked abnormalities such as cancer and diabetes. However, the disposition pathways, pharmacological targets and safety profiles of most Chinese herbal medicines are unknown or not well characterized. The evidence for the use of Chinese herbal medicines as effective and safe multi-component therapeutics is not established. The quality control and standardization of these natural products still constitute a major challenge in their evidence-based clinical application. Recently, there is an increased interest in the incorporation of systems biology approaches and combined use of preclinical and clinical models in understanding the complex disposition pathways, multiple targets and toxicities of Chinese herbal medicines. Like synthetic drugs, Chinese herbal medicines are subject to similar ADME processes in the body like synthetic drugs. However, data are scant on the ADME of most Chinese herbal medicines. Thus, it is important to characterize ADME for both drugs and Chinese herbal medicines. My research team and collaborators have synthesized several small molecule novel compounds for cancer treatment, including 5,6-dimethylxanthenone-4-acetic acid (DMXAA, an antiangiogenic agent and TNF-( inducer) and SYUIQ-5, a novel telomerase inhibitor. The metabolic pathways and transport properties of both DMAA and SYUIQ-5 have been characterized. We have also investigated the metabolism and transport of the major active components of several commonly used Chinese herbal medicines, such as Danshen (Salvia miltiorrhiza) and ginkgo (Ginkgo biloba) using a combination of in vitro and in vivo models. It is believed that ADME studies are necessary and important for both synthetic drugs and Chinese herbal medicines in an attempt to establish their efficacy and safe-ty profiles.
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