Quantitative prediction of in vivo drug-drug interactions based on in vitro inhibition or/and induction data for CYP3A4 / 药学学报

Inhibition or/and induction of CYP3A4 are the major mechanisms underlying the common clinical drug-drug interactions, which has been gained attention in new drug discovery and development as well as clinical practice. Quantitative prediction of drug-drug interactions at the early stage of drug development is advantageous for reducing the cost and duration of development and providing more information for the later clinical studies. The review summarizes the update progress on quantitative prediction of in vivo drug-drug interactions derived from models based on in vitro inhibition or/and induction for CYP3A4.

Interactions of intestinal H~+/oligopeptide cotransporter PEPT1 with drugs and regulation by affecting factors / 中国临床药理学与治疗学

H+/oligopeptide cotransporter PEPT1 mainly located at the brush border membrane of intestinal epithelium cell. transports dipeptide/tripeptide which is the degradation products of protein in digestive tract. Peptide-like drugs such as ?-lactam antibiotics,angiotensin-converting enzyme inhibitor (ACEI) and non-peptide drugs valaciclovir also can be transported and uptaked by PEPT1. PEPT1 is important for maintaining the homeostasis and the absorption of drugs in gastrointestinal tract. With the further research of PEPT1 gene, protein structure, and functional activity, we have known the factors about regulation of PEPT1 expression in membrane, their functional activities and substrate affinities. Some associated mechanism of regulation have been studied. As the wide substrate specificities of PEPT1, it becomes the target molecular on drug development and implication for drug delivery. Studies about interactions of PEPT1 with drugs are important for knowing the interactions of drugs, evaluating bioavailability of drug by intestinal absorption, researching the target treatment in anti-tumor drugs and individualization administration.