Poly ADP-ribose polymerase inhibitors (PARPi), which approved in recent years, are recommended for ovarian cancer, breast cancer, pancreatic cancer, prostate cancer and other cancers by The National Comprehensive Cancer Network (NCCN) and Chinese Society of Clinical Oncology (CSCO) guidelines. Because most of PARPi are metabolized by cytochrome P450 enzyme system, there are extensive interactions with other drugs commonly used in cancer patients. By setting up a consensus working group including pharmaceutical experts, clinical experts and methodology experts, this paper forms a consensus according to the following steps: determine clinical problems, data retrieval and evaluation, Delphi method to form recommendations, finally formation expert opinion on PARPi interaction management. This paper will provide practical reference for clinical medical staff.
Male ; Female ; Humans ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology* ; Consensus ; Ovarian Neoplasms/drug therapy* ; Drug Interactions ; Adenosine Diphosphate Ribose/therapeutic use*

The prognosis of infectious diseases is determined by host-pathogen interactions. Control of pathogens has been the central dogma of treating infectious diseases in modern medicine, but the pathogen-directed medicine is facing significant challenges, including a lack of effective antimicrobials for newly emerging pathogens, pathogen drug resistance, and drug side effects. Here, a mathematic equation (termed equation of host-pathogen interactions, HPI-Equation) is developed to dissect the key variables of host-pathogen interactions. It shows that control of pathogens does not necessarily lead to host recovery. Instead, a combination of promoting a host's power of self-healing and balancing immune responses provides the best benefit for host. Moreover, the HPI-Equation elucidates the scientific basis of traditional Chinese medicine (TCM), a host-based medicine that treats infectious diseases by promoting self-healing power and balancing immune responses. The importance of self-healing power elucidated in the HPI-Equation is confirmed by recent studies that the tolerance mechanism, which is discovered in plants and animals and conceptually similar to self-healing power, improves host survival without directly attacking pathogens. In summary, the HPI-Equation describes host-pathogen interactions with mathematical logic and precision; it translates the ancient wisdoms of TCM into apprehensible modern sciences and opens a new venue for integrating TCM and modern medicine for a future medicine. Sun J. A mathematic equation derived from host-pathogen interactions elucidates the significance of integrating modern medicine with traditional Chinese medicine to treat infectious diseases. J Integr Med. 2023; 21(4):324-331.
Animals ; Medicine, Chinese Traditional ; Communicable Diseases/drug therapy* ; Mathematics ; Host-Pathogen Interactions ; Drugs, Chinese Herbal/therapeutic use*

Mutations in the epithelial growth factor receptor (EGFR) is a driving factor that causes non-small cell lung carcinoma (NSCLC). The epithelial growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a crucial discovery in the treatment of lung cancer, particularly the efficacy of EGFR-TKIs is superior to that of the standard chemotherapy for patients with EGFR mutation-positive advanced NSCLC. Patients with NSCLC use EGFR-TKIs and other medications simultaneously is commonly seen, especially among those with comorbidities, which increases the risk of drug-drug interactions (DDIs) of EGFR-TKIs. The most common mechanisms underlying the DDIs of EGFR-TKIs are modulations of cytochrome P450 (CYP) and drug transporters [including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)], as well as gastrointestinal acid-inhibitory drugs [proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RA)]. Inhibitors or inducers of CYP enzymes and drug transporters can inhibit or accelerate the metabolism of EGFR-TKIs, which increase or reduce the exposure of EGFR-TKIs, thereby affect the efficacy and safety of EGFR-TKIs. In addition, PPIs or H(2)RA can decrease the solubility, bioavailability and efficacy of EGFR-TKIs. This review summarizes the mechanisms of DDIs of gefitinib, erlotinib, icotinib, afatinib, dacomitinib and osimertinib; the management recommendations for DDIs of those EGFR-TKIs from the Chinese and global guideline, as well as from the recent pre-clinical and clinical studies, which provide the reference and evidence for managing the combination therapies of EGFR-TKIs and other medications in clinics.
ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Drug Interactions ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Neoplasm Proteins/metabolism* ; Protein Kinase Inhibitors/adverse effects*

Cardiovascular diseases are a global public health problem, and the combination of Chinese and western medicine tends to be a major solution in China. However, the complex components in traditional Chinese medicine may interact with the therapeutic western medicines for the diseases, which will lead to the herb-drug interaction(HDI). The information on the interaction can serve as a reference for the rational combination of the Chinese and western medicines in the clinical treatment of cardiovascular diseases and help avoid the occurrence of clinical safety events. However, the research on the interaction of Chinese medicine is limited as compared with that on western medicine, and no systematic review on HDI in the treatment of cardiovascular diseases is available. Therefore, this study first introduced the mechanism of HDI, then summarized the research on HDI for the commonly used drugs for cardiovascular diseases, analyzed the problems in the available studies, and put forward suggestions on the application, regulation, and research. This study aims to highlight HDI in clinical drug use and provide a reference for rational use of combination of Chinese and western medicines in the treatment of cardiovascular diseases.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Cardiovascular Diseases/drug therapy* ; Herb-Drug Interactions ; Medicine, Chinese Traditional ; China

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occasioned worldwide alarm. Globally, the number of reported confirmed cases has exceeded 84.3 million as of this writing (January 2, 2021). Since there are no targeted therapies for COVID-19, the current focus is the repurposing of drugs approved for other uses. In some clinical trials, antiviral drugs such as remdesivir (Grein et al., 2020), lopinavir/ritonavir (LPV/r) (Cao et al., 2020), chloroquine (Gao et al., 2020), hydroxychloroquine (Gautret et al., 2020), arbidol (Wang et al., 2020), and favipiravir (Cai et al., 2020b) have shown efficacy in COVID-19 patients. LPV/r combined with arbidol, which is the basic regimen in some regional hospitals in China including Zhejiiang Province, has shown antiviral effects in COVID-19 patients (Guo et al., 2020; Xu et al., 2020). A retrospective cohort study also reported that this combination therapy showed better efficacy than LPV/r alone for the treatment of COVID-19 patients (Deng et al., 2020).
Animals ; COVID-19/drug therapy* ; Drug Interactions ; Drug Therapy, Combination ; Female ; Indoles/pharmacokinetics* ; Lopinavir/pharmacokinetics* ; Male ; Rats ; Retrospective Studies ; Ritonavir/pharmacokinetics* ; SARS-CoV-2

In this study, we explored the antibacterial effect and mechanism of dihydroartemisinin(DHA) combined with cefuroxime(CFX) or ampicillin against Escherichia coli. The minimum inhibitory concentration(MIC) of DHA, cefuroxime, and ampicillin against E. coli was 300,25,25 μmol·L~(-1), respectively, determined by broth microdilution method and 2,3,5-triphenyltetrazolium chloride(TTC) method. The minimum bactericidal concentration(MBC) was 25 μmol·L~(-1) for cefuroxime, above 600 μmol·L~(-1) for DHA. The fractional inhibitory concentration index(FICI) of DHA combined with cefuroxime or ampicillin was 0.375 and 0.75, respectively, determined by checkerboard microdilution assay, suggesting the synergistic effect or additive effect of the drug combination. Moreover, the time-effect curve showed that the antibacterial activity of DHA and CFX combination was much stronger than that of either of the drugs, suggesting that combination with DHA can decrease the CFX dosage. Then we studied the synergistic mechanism of DHA combined with cefuroxime and found that the combination of the two drugs had a significant inhibitory effect on the total protein bands, as shown by the results of polypropylene gel electrophoresis. The results of conductivity method and alkaline phosphatase test respectively showed that its conductivity value and alkaline phosphatase(AKP) leak were significantly higher than either of the drugs, suggesting that the integrity of bacteria may be damaged. The scanning electron microscope(SEM) results showed that the morphology of E. coli was destroyed most in the combination group. The quantitative fluorescence PCR technology showed that the combination of two drugs can inhibit the expression of superoxide stress gene soxS. In summary, the combination of dihydroartemisinin and cefuroxime has a synergistic antibacterial effect on E. coli.
Anti-Bacterial Agents ; Artemisinins ; Cefuroxime ; Drug Synergism ; Escherichia coli ; Microbial Sensitivity Tests

Depression is a common affective disorder. The application of antidepressants can significantly alleviate the symptoms of depression, which is the most important way to treat depression in clinical practice. Due to the complex etiology, wide variety, as well as diversity and severity of serious concomitant symptoms, rational addition of other drugs into antidepressants can significantly improve the cure rates of depression, reduce adverse reactions, and improve patient compliances. Therefore, the combined applications of differential drugs have been commonly used in clinic. In this paper, more than 600 literatures about depression from 2010 to 2019 were collected based on the key words of antidepressant, depression, combined medication, synergism and increase efficiency. Based on this, by summarizing and classifying the existing combinations of antidepressant drugs, this paper systematically expounds the current combined applications of antidepressant drugs in three categories, i.e. western medicines combined with western medicines, western medicines combined with traditional Chinese medicines, and traditional Chinese medicines combined with traditional Chinese medicines, in the expectation of providing the direction and basis for the selection of rational combinations of antidepressant drugs in clinic.
Antidepressive Agents ; Drug Interactions ; Humans ; Medicine, Chinese Traditional

The purpose of this study was to investigate the effect of apigenin on UGT1 A1 enzyme activity and to predict the potential drug-drug interaction of apigenin in clinical use. First,on the basis of previous experiments,the binding targets and binding strength of apigenin to UGT1 A1 enzyme were predicted by computer molecular docking method. Then the inhibitory effect of apigenin on UGT1 A1 enzyme was evaluated by in vitro human liver microsomal incubation system. Molecular docking results showed that apigenin was docked into the active region of UGT1 A1 enzyme protein F,consistent with the active region of bilirubin docking,with moderate affinity. Apigenin flavone mother nucleus mainly interacted with amino acid residues ILE343 and VAL345 to form hydrophobic binding Pi-Alkyl. At the same time,the hydroxyl group on the mother nucleus and the amino acid residue LYS346 formed an additional hydrogen bond,which increased the binding of the molecule to the protein. These results suggested that the flavonoid mother nucleus structure had a special structure binding to the enzyme protein UGT1 A1,and the introduction of hydroxyl groups into the mother nucleus can increase the binding ability. In vitro inhibition experiments showed that apigenin had a moderate inhibitory effect on UGT1 A1 enzyme in a way of competitive inhibition,which was consistent with the results of molecular docking. The results of two experiments showed that apigenin was the substrate of UGT1 A1 enzyme,which could inhibit the activity of UGT1 A1 enzyme competitively,and there was a risk of drug interaction between apigenin and UGT1 A1 enzyme substrate in clinical use.
Apigenin/chemistry* ; Bilirubin/chemistry* ; Drug Interactions ; Glucuronosyltransferase/metabolism* ; Humans ; Hydrogen Bonding ; Microsomes, Liver/drug effects* ; Molecular Docking Simulation

Herbal products have been used for therapeutic purposes for a long time. However, many herbs can be toxic and even life-threatening. If refractory ventricular tachycardia (VT) is caused by herbal products and shows no response to conventional therapy, intravenous lipid emulsion (ILE) therapy can be considered. We report a case of herbal intoxication leading to refractory VT, which was successfully treated with ILE therapy. A 36-year-old woman with aplastic anemia presented with mental changes. She had taken an unknown herbal decoction three days before visiting the hospital. Soon after coming to the hospital, she went into cardiac arrest. Cardiopulmonary resuscitation was performed, and return of spontaneous circulation with VT was achieved. Synchronized cardioversion was then performed and amiodarone was administered. However, VT with pulse continued, so ILE therapy was attempted, which led to the resolution of VT.
Adult ; Amiodarone ; Anemia, Aplastic ; Cardiopulmonary Resuscitation ; Electric Countershock ; Fat Emulsions, Intravenous ; Female ; Heart Arrest ; Herb-Drug Interactions ; Humans ; Tachycardia, Ventricular

OBJECTIVES: To address and elucidate the impact of pharmacist-led home medicines review (HMR) services on identifying drug-related problems (DRPs) among the elderly population in home care settings.METHODS: A comprehensive systematic search was performed using electronic scientific databases such as PubMed, Scopus, Embase, and Web of Science for studies published between January 1, 2008 and December 31, 2018, pertaining to HMR services by pharmacists for identifying DRPs.RESULTS: In total, 4,292 studies were retrieved from the searches, of which 24 were excluded as duplicates. Titles and abstracts were screened for the remaining 4,268 studies, of which 4,239 were excluded due to the extraneous nature of the titles and/or abstracts. Subsequently, 29 full-text articles were assessed, and 19 were removed for lacking the outcome of interest and/or not satisfying the study's inclusion criteria. Finally, 10 studies were included in the review; however, publication bias was not assessed, which is a limitation of this study. In all studies, pharmacists identified a highly significant amount of DRPs through HMR services. The most common types of DRPs were potential drug-drug interactions, serious adverse drug reactions, need for an additional drug, inappropriate medication use, non-adherence, untreated indications, excessive doses, and usage of expired medications.CONCLUSIONS: HMR is a novel extended role played by pharmacists. The efficiency of such programs in identifying and resolving DRPs could minimize patients' health-related costs and burden, thereby enhancing the quality of life and well-being among the elderly.
Aged ; Drug Interactions ; Drug-Related Side Effects and Adverse Reactions ; Frail Elderly ; Home Care Services ; Humans ; Pharmacists ; Publication Bias ; Quality of Life