Dual status refers to normal physiological state and abnormal disease state. In the process of new drug development, pharmacokinetic research has always played an important role from early screening and preclinical research to clinical research and post-marketing evaluation. However, preclinical pharmacokinetic data are mainly derived from healthy animals, which is unreasonable. On the one hand, patients are the final consumers of drugs because drugs are mainly used to treat patients with diseases. On the other hand, whether the body is in a pathological state and the severity of the disease have different effects on the absorption, distribution, metabolism, and excretion (ADME) of drugs, which is closely related to whether the clinical drug is safe and effective. Therefore, studying the pharmacokinetics in disease states is more meaningful and clinically relevant.
It's well known that the tissues and organs of the body will be damaged to different degrees in the disease state when compared with the normal state. For example, the metabolic function of the liver in patients with liver injury is reduced. The activity of metabolic enzymes in diabetic patients is changed. The type and quantity of intestinal flora in patients with rheumatoid arthritis are altered. The permeability of tract cells in patients with irritable bowel syndrome will be reduced. And the above changes have affected the pharmacokinetic process of the drug, thereby altering the bioavailability of the drug. In the process of disease occurrence and development, the intestinal flora and cell membrane permeability will not only be changed, but also the drug metabolizing enzymes and transporters related to drug metabolism and disposal are affected by abnormal regulation, and its possible mechanisms mainly involve inflammation-related signaling pathways/nuclear receptors, epigenetic modification and protein post-translational modification, etc., which result in changes in the pharmacokinetic behavior of drugs, drug efficacy, and toxicity. Therefore, we should pay more attention to the regulatory mechanisms that cause the pharmacokinetic differences of drugs in the dual status organism.
Given the fact that drugs are mainly used in the body under disease states, this topic focuses on pharmacokinetic differences of drugs and their regulatory mechanisms under dual status including normal and diseased organisms. We hope to optimize the drug evaluation system based on disease states, individualized safety provides reference and ideas for effective drug use. In this Research Topic, we welcome original research, reviews, and mini reviews articles, including but not limited to the following subjects:
•The pharmacokinetic differences of drug including Chinese medicine and their mechanisms under normal and disease status.
• The changes in the expression and function of drug-metabolizing enzymes and drug transporters in disease status and their related regulatory mechanisms.
•The study of intestinal microbiome mediated drug metabolism and its effect on drug efficacy and toxicity.
• ADME/toxicity of drugs as well as their regulation, drug-drug interactions mediated by nuclear receptors, transporters and metabolic enzymes based on the methods and techniques of pharmacokinetics, transcriptomics, and metabolomics.
• The study of drug pharmacokinetic-pharmacodynamic (PK-PD) link model under disease status.
Dual status refers to normal physiological state and abnormal disease state. In the process of new drug development, pharmacokinetic research has always played an important role from early screening and preclinical research to clinical research and post-marketing evaluation. However, preclinical pharmacokinetic data are mainly derived from healthy animals, which is unreasonable. On the one hand, patients are the final consumers of drugs because drugs are mainly used to treat patients with diseases. On the other hand, whether the body is in a pathological state and the severity of the disease have different effects on the absorption, distribution, metabolism, and excretion (ADME) of drugs, which is closely related to whether the clinical drug is safe and effective. Therefore, studying the pharmacokinetics in disease states is more meaningful and clinically relevant.
It's well known that the tissues and organs of the body will be damaged to different degrees in the disease state when compared with the normal state. For example, the metabolic function of the liver in patients with liver injury is reduced. The activity of metabolic enzymes in diabetic patients is changed. The type and quantity of intestinal flora in patients with rheumatoid arthritis are altered. The permeability of tract cells in patients with irritable bowel syndrome will be reduced. And the above changes have affected the pharmacokinetic process of the drug, thereby altering the bioavailability of the drug. In the process of disease occurrence and development, the intestinal flora and cell membrane permeability will not only be changed, but also the drug metabolizing enzymes and transporters related to drug metabolism and disposal are affected by abnormal regulation, and its possible mechanisms mainly involve inflammation-related signaling pathways/nuclear receptors, epigenetic modification and protein post-translational modification, etc., which result in changes in the pharmacokinetic behavior of drugs, drug efficacy, and toxicity. Therefore, we should pay more attention to the regulatory mechanisms that cause the pharmacokinetic differences of drugs in the dual status organism.
Given the fact that drugs are mainly used in the body under disease states, this topic focuses on pharmacokinetic differences of drugs and their regulatory mechanisms under dual status including normal and diseased organisms. We hope to optimize the drug evaluation system based on disease states, individualized safety provides reference and ideas for effective drug use. In this Research Topic, we welcome original research, reviews, and mini reviews articles, including but not limited to the following subjects:
•The pharmacokinetic differences of drug including Chinese medicine and their mechanisms under normal and disease status.
• The changes in the expression and function of drug-metabolizing enzymes and drug transporters in disease status and their related regulatory mechanisms.
•The study of intestinal microbiome mediated drug metabolism and its effect on drug efficacy and toxicity.
• ADME/toxicity of drugs as well as their regulation, drug-drug interactions mediated by nuclear receptors, transporters and metabolic enzymes based on the methods and techniques of pharmacokinetics, transcriptomics, and metabolomics.
• The study of drug pharmacokinetic-pharmacodynamic (PK-PD) link model under disease status.