1.
Gut microbiota as an "invisible organ" that modulates the function of drugs.
Li, X, Liu, L, Cao, Z, Li, W, Li, H, Lu, C, Yang, X, Liu, Y
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2020;:109653
Abstract
Gut microbiota plays an important role in the gut and have become a hotspot of recent research interests. Commensal microbiota in gut exert a variety of effects on the host, from shaping the structure and function of the gut and the immune system to the modulation of nutrient status of the host and the treatment outcomes of some drugs. Gut microbiota and its enzyme product and subsequent products, such as short-chain fatty acid and bile acid, play important roles in the biotransformation of drugs via directly or indirectly affecting drug absorption, toxicity, metabolism and bioavailability. Drugs, especially antibiotics, also affect the homeostasis of probiotics and the integrity and function of the intestinal mucosa. These interplaying processes produce a variety of important metabolites of the host and drugs and affect the balance of microbiota and the mucosal barrier then modulate the function of drugs. Gut microbiota imbalance is associated with a broad range of disease mechanisms, and this association denotes a new drug-therapeutic avenue. The present review summarizes how gut microbiota acts as an "invisible organ" to directly or indirectly modulate the function of drugs, on the aspects of probiotic homeostasis, drugs and host nutritional metabolism, AJC, mucus layer and microfold cells.
2.
Assessment of Pharmacokinetic Drug-Drug Interactions in Humans: In Vivo Probe Substrates for Drug Metabolism and Drug Transport Revisited.
Fuhr, U, Hsin, CH, Li, X, Jabrane, W, Sörgel, F
Annual review of pharmacology and toxicology. 2019;:507-536
Abstract
Pharmacokinetic parameters of selective probe substrates are used to quantify the activity of an individual pharmacokinetic process (PKP) and the effect of perpetrator drugs thereon in clinical drug-drug interaction (DDI) studies. For instance, oral caffeine is used to quantify hepatic CYP1A2 activity, and oral dagibatran etexilate for intestinal P-glycoprotein (P-gp) activity. However, no probe substrate depends exclusively on the PKP it is meant to quantify. Lack of selectivity for a given enzyme/transporter and expression of the respective enzyme/transporter at several sites in the human body are the main challenges. Thus, a detailed understanding of the role of individual PKPs for the pharmacokinetics of any probe substrate is essential to allocate the effect of a perpetrator drug to a specific PKP; this is a prerequisite for reliably informed pharmacokinetic models that will allow for the quantitative prediction of perpetrator effects on therapeutic drugs, also in respective patient populations not included in DDI studies.