Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention  

作　　者：Sujit Nair Ah-Ng Tony Kong 

机构地区：[1]Amrita Cancer Discovery Biology Laboratory, Amrita Vishwa Vidyapeetham University [2]Center for Cancer Chemoprevention Research and Department of Pharmaceutics, Rutgers, The State University of New Jersey

出　　处：《Journal of Chinese Pharmaceutical Sciences》2016年第1期12-22,共11页中国药学（英文版）

基　　金：Institutional funds from Amrita Vishwa Vidyapeetham University,India,and Rutgers;the State University of New Jersey,USA;RO1 CA118947 and RO1 CA152826 from the National Institutes of Health(NIH),USA

摘　　要：Sulforaphane(SFN), found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There is great enthusiasm for bench-to-bedside development of SFN as a potent chemopreventive agent, possibly alone or as an adjunct to existing chemotherapy regimens, in the oncology care setting to reduce toxicity of chemotherapeutics and potentially enhance their cancer cell-kill efficacy. In this review, we appreciate existing knowledge on SFN using a pharmacometrics approach, which is fast becoming a gold standard in discovery research and validation of New Chemical Entities and New Biological Entities in pharmaceutical industry. We discuss the epistemology of SFN target engagement and quantitative systems pharmacology with due emphasis on mechanistic pharmacology, pharmacodynamics, pharmacogenomics and metabolism of SFN. In addition, we explore the quantitative freeway to SFN translational medicine by assessing the preclinical and clinical PK/metabolism aspects of SFN that form the cornerstone of SFN pharmacometric evaluation, as well as the promise of SFN in prostate cancer. Taken together, we share perspectives on the exciting developments in translational cancer chemoprevention, with emphasis on the pharmacometric aspects, of the nutraceutical SFN which is currently in clinical trials, and suggest that the pharmacometric approach holds great promise in the SFN translational pharmacology paradigm for prostate cancer.Sulforaphane（SFN）, found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There is great enthusiasm for bench-to-bedside development of SFN as a potent chemopreventive agent, possibly alone or as an adjunct to existing chemotherapy regimens, in the oncology care setting to reduce toxicity of chemotherapeutics and potentially enhance their cancer cell-kill efficacy. In this review, we appreciate existing knowledge on SFN using a pharmacometrics approach, which is fast becoming a gold standard in discovery research and validation of New Chemical Entities and New Biological Entities in pharmaceutical industry. We discuss the epistemology of SFN target engagement and quantitative systems pharmacology with due emphasis on mechanistic pharmacology, pharmacodynamics, pharmacogenomics and metabolism of SFN. In addition, we explore the quantitative freeway to SFN translational medicine by assessing the preclinical and clinical PK/metabolism aspects of SFN that form the cornerstone of SFN pharmacometric evaluation, as well as the promise of SFN in prostate cancer. Taken together, we share perspectives on the exciting developments in translational cancer chemoprevention, with emphasis on the pharmacometric aspects, of the nutraceutical SFN which is currently in clinical trials, and suggest that the pharmacometric approach holds great promise in the SFN translational pharmacology paradigm for prostate cancer.

关 键 词：PHARMACOMETRICS Pharmacokinetics Quantitative systems pharmacology Target engagement Metabolism PHARMACOGENOMICS Chemoprevention SULFORAPHANE ISOTHIOCYANATE Prostate cancer 

分 类 号：R962[医药卫生—药理学]