Classification of natural products as sources of drugs according to the biopharmaceutics drug disposition classification system(BDDCS)

Natural products(NPs) are compounds that are derived from natural sources such as plants, animals, and microisms. Therapeutics has benefited from numerous drug classes derived from natural product sources. The Biopharmaceutics Drug position Classification System(BDDCS) was proposed to serve as a basis for predicting the importance of transporters and enzymes in determining drug bioavailability and disposition. It categorizes drugs into one of four biopharmaceutical classes according to their water solubility and extent of metabolism. The present paper reviews 109 drugs from natural product sources: 29% belong to class 1(high solubility, extensive metabolism), 22% to class 2(low solubility, extensive metabolism), 40% to class 3(high solubility, poor metabolism), and 9% to class 4(low solubility, poor metabolism). Herein we evaluated the characteristics of NPs in terms of BDDCS class for all 109 drugs as wells as for subsets of NPs drugs derived from plant sources as antibiotics. In the 109 NPs drugs, we piled 32 drugs from plants, 50%(16) of total in class 1, 22%(7) in class 2 and 28%(9) in class 3, none found in class 4; Meantime, the antibiotics were found 5(16%) in class 2, 22(71%) in class 3, and 4(13%) in class 4; no drug was found in class 1. Based on this classification, we anticipate BDDCS to serve as a useful adjunct in evaluating the potential characteristics of new natural products.

Preclinical experimental models of drug metabolism and disposition in drug discovery and development

Drug discovery and development involve the utilization of in vitro and in vivo ex perimental models.Different models,ranging from test tube experiments to cell cultures,animals,healthy human subjects,and even small numbers of patients that are involved in clinical trials,are used at different stages of drug discovery and development for determination of efficacy and safety.The proper selection and applications of correct models,as well as appropriate data interpretation,are critically important in decision making and succesful advancement of drug candidates.In this review,we discuss strategies in the applications of both in vitro and in vivo.experimental models of drug metabolism and disposition.

Construction and characterization of a humanized SLCO1B1 rat model with its application in evaluating the uptake of different statins

Organic anion-transporting polypeptides IB1(OATPIB1)plays a crucial role in the transport of statins.However,there are too few animal models related to OATPIB1,especially humanized animal models.In this study,the human SLCOIB1 cDNA was inserted into the second exon of the rat Slcolb2 gene using CRISPR/Cas9 technology.Pharmacokinetic characteristics of statins were conducted in wild-type(WT),humanized OATPIB1(hOATPIB1),and OATPIB2 knockout(OATPIB2 KO)rats,respec-tively.The results showed that human OATPIB1 was successfully expressed in rat liver and exhibited transport function.Furthermore,the pharmacokinetic results revealed that OATPIB1 exhibited varying uptake levels of pivastatin,rosuvastatin,and fluvastatin,leading to different levels of exposure within the body.These results were consistent with those obtained from in vitro experiments using overexpressed cell lines.In conclusion,we established a novel humanized SLCOIBI transgenic rat model to assess the role of human OATPIB1 in the uptake of different statins.The different uptake mediated by OATPIB1 may be an important reason for the different efficacy of statins.The hOATPIB1 rat is a promising model for improving the prediction of human drug transport.