Antiretroviral therapy is the recognized treatment for human immunodeficiency virus (HIV) infection involving several antiviral agents. Even though highly active antiretroviral therapy has been proven to be very effective in suppressing HIV replication, the antiretroviral drugs, belonging to different pharmacological classes, present quite complex pharmacokinetic properties such as extensive drug metabolism and transport by membrane-associated drug carriers. Moreover, due to uncomplications or complications in HIV-infected populations, an antiretroviral-based multiple-drug coadministration therapy strategy is usually applied for treatment effect, thus raising the possibility of drugdrug interactions between antiretroviral drugs and common drugs such as opioids, stains, and hormonal contraceptives. Herein, thirteen classical antiretroviral drugs approved by US Food and Drug Administration were summarized. Besides, relative drug metabolism enzymes and transporters known to interact with those antiretroviral drugs were detailed and described. Furthermore, one after the summarized antiretroviral drugs, the drug-drug interactions between two antiretroviral drugs or antiretroviral drug - conventional medical drugs of the past decade were discussed and summarized. This review is intended to deepen the pharmacological understanding of antiretroviral drugs and promote more secure clinical applications for antiretroviral drugs to treat HIV.

INTRODUCTION: It is well known that the response to and metabolism of the drugs entering the human body varies widely across individuals. One of the reasons is that such interpersonal differences may be related to gut microbes. On one hand, drugs or xenobiotics entering the human body may affect the composition of the gut microbiome; on the other hand, the gut microbiota may alter the absorption, distribution, metabolism and excretion (abbreviated as ADME) process of drugs or xenobiotics vice versa. However, the majority of studies focused on the interaction of general population cohorts with the gut microbiota, which is incompatible with the real clinic. For example, the gut microbiota is closely associated with the progression and treatment of irritable bowel syndrome, a common functional disorder of the gastrointestinal tract. Under the disease status, the composition of the gut microbiota is altered affecting the pharmacokinetics, efficacy and toxicity of xenobiotics. Concerning irritable bowel syndrome, a few studies reported that the xenobiotics administration process was gut microbial-mediated, while it also affected drug efficacy and toxicity. Thus, the correlation between gut microbiota and xenobiotics administration, especially the drugs administered, should be elucidated. METHOD: This review paper links differences between the gut microbiome and drug metabolism, which play a significant role in the implications for medical therapy and drug development in irritable bowel syndrome indications. RESULT: The human intestinal microbiota permeates the ADME process of orally administered drugs and has the potential to further modify the efficacy and toxicity of agents through the mediation of various enzymes, while at the same time, medications could also alter the composition and function of the human intestinal microbiota.

Therapeutic antisense oligonucleotides (ASOs) represent a diverse array of chemically modified singlestranded deoxyribonucleotides that work complementarily to affect their mRNA targets. They vastly differ from conventional small molecules. These newly developed therapeutic ASOs possess unique absorption, distribution, metabolism, and excretion (ADME) processes that ultimately determine their pharmacokinetic, efficacy and safety profiles. The ADME properties of ASOs and associated key factors have not been fully investigated. Therefore, thorough characterization and in-depth study of their ADME properties are critical to support drug discovery and development processes for safe and effective therapeutic ASOs. In this review, we discussed the main factors affecting the ADME characteristics of these novels and evolving therapies. The major changes to ASO backbone and sugar chemistry, conjugation approaches, sites and routes of administration, etc., are the principal determinants of ADME and PK profiles that consequentially impact their efficacy and safety profiles. In addition, species difference and DDI considerations are important in understanding ADME profile and PK translatability but are less studied for ASOs. We, therefore, have summarized these aspects based on current knowledge and provided discussions in this review. We also give an overview of the current tools, technologies, and approaches available to investigate key factors that influence the ADME of ASO drugs and provide future perspectives and knowledge gap analysis.

Atherosclerosis (AS) is one of the major risk factors for cardiovascular disease pathogenesis, and current studies have found that the development of atherosclerosis is closely related to the intestinal microbiome. This review describes the relationship between the development of atherosclerosis and the gut microbiome with its metabolites and reviews the interactions between atherosclerosis-related drugs and the intestinal microbiome, especially the in vivo metabolic effects of the intestinal microbiome on drugs related to the treatment of atherosclerosis, to provide further understanding for the development of drugs based on the intestinal microbiome to treat atherosclerosis.