Current Drug Metabolism - Volume 21, Issue 12, 2020

The clinical application of herbal medicines is increasing, but there is still a lack of comprehensive safety data and in-depth research into mechanisms of action. The composition of herbal medicines is complex, with each herb containing a variety of chemical components. Each of these components may affect the activity of metabolizing enzymes, which may lead to herb-drug interactions. It has been reported that the combined use of herbs and drugs can produce some unexpected interactions. Therefore, this study reviews the progress of research on safety issues caused by the effects of herbs on metabolizing enzymes with reference to six categories of drugs, including antithrombotic drugs, non-steroidal anti-inflammatory drugs, anti-diabetic drugs, statins lipid-lowering drugs, immunosuppressants, and antineoplastic drugs. Understanding the effects of herbs on the activity of metabolizing enzymes could help avoid the toxicity and adverse drug reactions resulting from the co-administration of herbs and drugs, and help doctors to reduce the risk of prescription incompatibility.

As a kind of haemoglobin, cytochrome P450 enzymes (CYP450) participate in the metabolism of many substances, including endogenous substances, exogenous substances and drugs. It is estimated that 60% of common prescription drugs require bioconversion through CYP450. The influence of macrolides on CYP450 contributes to the metabolism and drug-drug interactions (DDIs) of macrolides. At present, most studies on the effects of macrolides on CYP450 are focused on CYP3A, but a few exist on other enzymes and drug combinations, such as telithromycin, which can decrease the activity of hepatic CYP1A2 and CYP3A2. This article summarizes some published applications of the influence of macrolides on CYP450 and the DDIs of macrolides caused by CYP450. And the article may subsequently guide the rational use of drugs in clinical trials. To a certain extent, poisoning caused by adverse drug interactions can be avoided. Unreasonable use of macrolide antibiotics may enable the presence of residue of macrolide antibiotics in animal-origin food. It is unhealthy for people to eat food with macrolide antibiotic residues. So it is of great significance to guarantee food safety and protect the health of consumers by the rational use of macrolides. This review gives a detailed description of the influence of macrolides on CYP450 and the DDIs of macrolides caused by CYP450. Moreover, it offers a perspective for researchers to further explore in this area.

Background: The anti-CD20 antibody rituximab, which promotes the selective depletion of CD20 positive B cells, was the first targeted therapy that was approved for the treatment of B-cell malignancies, and it is now widely prescribed in both malignant and non-malignant, immune-related diseases. However, the cause of its various clinical responses in certain diseases, have not been clearly elucidated. The variabilities in inter-individual pharmacokinetic and the emerging evidence of the relationships between pharmacokinetic and pharmacodynamic may provide a better understanding of this drug. Methods: We searched and summarized the latest published articles on rituximab pharmacokinetic profiles and the pharmacokinetic/pharmacodynamic models in different patient populations, including B-cell malignancies, rheumatoid arthritis, ANCA-associated vasculitis, and glomerular kidney diseases. Results: Most pharmacokinetic data are drawn from clinical studies in oncology clinical practice. Body weight, gender, and antigen-related factors are proven to be the key factors affecting rituximab pharmacokinetics. In addition, the positive exposure-response relations were reported, which provide encouraging evidence for individualized therapies. While in immune disorders, especially in the off-labeled indications, pharmacokinetic studies are quite limited. Compared with that in B-cell malignancies, the differences in the pharmacokinetic parameters may be attributed to the different pathogeneses of diseases, mechanisms of action and dosing strategies. However, the correlation between drug exposure and clinical outcomes remains unclear. Conclusion: Here, we provide an overview of the complexities associated with rituximab pharmacokinetics and pharmacodynamics in different diseases. Although many influencing factors need to be verified in future studies, a better understanding of the relationships between pharmacokinetic and pharmacodynamic may assist in optimizing rituximab clinical practice.

Background: Glucose is the main energy component of cellular activities. However, as a polar molecule, glucose cannot freely pass through the phospholipid bilayer structure of the cell membrane. Thus, glucose must rely on specific transporters in the membrane. Drugs with a similar chemical structure to glucose may also be transported through this pathway. Methods: This review describes the structure, distribution, action mechanism and influencing factors of glucose transporters and introduces the natural drugs mediated by these transporters and drug design strategies on the basis of this pathway. Results: The glucose transporters involved in glucose transport are of two major types, namely, Na+-dependent and Na+-independent transporters. Glucose transporters can help some glycoside drugs cross the biological membrane. The transmembrane potential is influenced by the chemical structure of drugs. Glucose can be used to modify drugs and improve their ability to cross biological barriers. Conclusion: The membrane transport mechanism of some glycoside drugs may be related to glucose transporters. Glucose modification may improve the oral bioavailability of drugs or achieve targeted drug delivery.

Background: Anthraquinones, rhein and aurantio-obtusin were isolated from the herb Duhaldea nervosa for the first time by our group, which were also found in plants that belong to the plant family Compositae. Anthraquinone compounds have a range of pharmacological activities such as anti-inflammatory, anti-cancer, antioxidation, anti-diabetes, etc. and can be used as a laxative, for liver protection, treatment of chronic renal failure, etc. However, in recent years, anthraquinones have been reported to be cytotoxic to the liver and kidneys. Therefore, it is very important to study the pharmacokinetics and metabolism of rhein and aurantio-obtusin, which are common ingredients in many traditional Chinese medicines (TCM). According to our research, the pharmacokinetics and metabolism of rhein and aurantio-obtusin are comprehensively summarized in the paper for the first time. Objective: The study provides comprehensive information on pharmacokinetics and metabolism of rhein and aurantio- obtusin in different Species; meanwhile, the aim of this review is also to provide a reference for a reasonable application of TCM enriched with these two ingredients. Methods: The metabolism and pharmacokinetics of rhein and aurantio-obtusin were searched by the Web of Science, PubMed, Google scholar and some Chinese literature databases. Results: Rhein and aurantio-obtusin exist mainly in the form of metabolites in the body. Rhein and aurantio-obtusin and its metabolites might be responsible for pharmacological effects in the body. Therefore, the significance of studying the in vivo metabolites of rhein and aurantio-obtusin is not only essential to clarify their pharmacological mechanism, but also to find new active compound ingredients. The metabolism of rhein is different in different species, so the toxicity effects of rhein may also be different after oral administration in different species; however, the metabolic profiles of aurantio-obtusin in the liver microsomes of different species are similar. Conclusion: This paper not only provides detail regarding the pharmacokinetics of rhein and aurantio-obtusin, but it is anticipated that it will also facilitate further study on the metabolism of rhein and aurantio-obtusin.

Background: With significant clinical effects, traditional Chinese medicine (TCM) has been attracting increasing interest of the world's scientific community. However, TCM contains immense amounts of chemical components. It is a great challenge to objectively evaluate the correlation between the in vivo process and the therapeutic effect of TCM. The purpose of this systematic review was to summarize the recent investigation (from 2017 to 2019) on preclinical pharmacokinetics (PK) of TCM via liquid chromatography coupled with mass spectrometry (LC-MS/MS). Methods: We reviewed the published articles regarding the PK of TCM by LC-MS/MS. In addition, we summarized information on PK parameter of bioactive components, single herb and traditional Chinese medicine prescriptions. Results: The vast majority of literature on preclinical PK of TCM uses single oral administration, the biological matrix is mostly rat plasma, and the main PK parameters include AUC, Cmax, Tmax and T1/2, etc. Conclusion: Although LC-MS/MS can be used for high-throughput analysis, the characterization of in vivo processes of TCM still has a long way. With the advantages of high sensitivity, high specificity and simple operation, the increasingly mature LC-MS/MS technology will play an important role in the PK study of TCM.

Objective: To study the compatibility regularity of Simiao Yong’an decoction by determining the plasma protein binding rate with the constituents in Simiao Yong’an decoction and to preliminarily clarify the effects of the compatibility on the plasma protein binding rate of different components. Methods: Based on the equilibrium dialysis method, high-performance liquid chromatography was used to determine the contents of six constituents, which were divided into a single group and combination groups, in Simiao Yong’an decoction in the internal and external dialysis solutions. The obtained plasma protein binding rate through calculations was an index to evaluate the binding of the above components to plasma protein in different conditions. Results: Harpagide, harpagoside, sweroside and loganin showed low plasma protein binding rates, ferulic acid exhibited a moderate plasma protein binding rate, and glycyrrhizic acid showed a high plasma protein binding rate. The compatibility study showed that glycyrrhizic acid promoted the binding of ferulic acid to plasma protein. Glycyrrhizic acid and ferulic acid were the key compounds to promote the binding of harpagide to plasma protein. Glycyrrhizic acid, harpagide, harpagoside and loganin had a significant inhibitory effects on the binding of sweroside to plasma protein. The plasma protein binding capacities of harpagoside and loganin were reduced by the other five constituents. Glycyrrhizic acid had the strongest plasma protein binding effect, and the binding effect was not affected by other components. Conclusion: This study explores the effects of compound compatibility on effective components from the perspective of plasma protein binding by high-performance liquid chromatography combined with the equilibrium dialysis method, and lays a foundation for clarifying the compatibility rule of Simiao Yong’an decoction and also provides a new idea for the study of the compatibility of traditional Chinese medicine formulas.