Clinical treatment and management of invasive fungal disease in recipients of solid organ transplantation / 器官移植

With widespread application of solid organ transplantation (SOT), the incidence of postoperative invasive fungal disease (IFD) in SOT recipients has been increased year by year. In recent years, the awareness of preventive antifungal therapy for SOT recipients has been gradually strengthened. However, the problem of fungal resistance has also emerged, leading to unsatisfactory efficacy of original standardized antifungal regimens. Drug-drug interaction and hepatorenal toxicity induced by drugs are also challenges facing clinicians. In this article, the characteristics of drug-drug interaction and hepatorenal toxicity among triazole, echinocandin and polyene antifungal drugs and immunosuppressants were reviewed, and postoperative preventive strategies for IFD in different types of SOT recipients and treatment strategies for IFD caused by infection of different pathogens were summarized, aiming to provide reference for physicians in organ transplantation and related disciplines.

Effects of disodium cantharidinate on the pharmacokinetic behavior of capecitabine in rats / 中国药房

OBJECTIVE To study the effects of disodium cantharidinate on the pharmacokinetic behavior of capecitabine in rats. METHODS Rats were randomly divided into two control groups and two experimental groups with 6 rats in each group. Two control groups were intraperitoneally injected with normal saline， and two experimental groups were intraperitoneally injected with Disodium cantharidinate injection of 0.5 mL/kg， for 7 consecutive days. Eight days after medication， control group 1 and experimental group 1 were given capecitabine 5 mg/kg intragastrically， while control group 2 and experimental group 2 were given capecitabine 5 mg/kg intravenously. Blood samples were collected at different time points after administration. After extraction with ethyl acetate， the concentration of capecitabine in rat plasma was determined by UPLC-MS/MS method using tolbutamide as the internal standard. The pharmacokinetic parameters were calculated by DAS 2.0 software. RESULTS Compared with control group 1， MRT0－∞， cmax， AUC0－30 h， AUC0－∞ and F of experimental group 1 were increased significantly， while CLz/F was decreased significantly （P＜0.01）. Compared with control group 2， t1/2， MRT0－30 h， MRT0-∞， AUC0－30 h and AUC0－∞ of experimental group 2 were increased significantly （P＜0.01）. CONCLUSIONS Disodium cantharidinate can increase the plasma exposure of capecitabine in rats， improve its oral bioavailability， prolong the average residence time， and reduce its clearance rate.

Using Package Inserts to Disseminate Information Regarding Drug Interactions Mediated by CYP3A Inhibition: Status and Issues / 医薬品情報学

Objective: In Japan, the Guideline on Drug Interaction for Drug Development and Appropriate Provision of Information (GL) was notified in 2018. In the GL and the associated document, it was determined that package inserts of drugs which need to be categorized as precaution due to the significant degree of drug interactions by CYP3A inhibition should describe possible perpetrator drugs using designated expressions, such as “strong CYP3A inhibitor.” For contraindication, it was decided that all drugs should be described individually. In 2021, as supplementary information to the GL, a list of CYP substrates, inhibitors and inducers, classified based on interaction strength and CYP isoenzymes (i.e., the drug list), was published. In this study, we aimed to survey the information on drug interactions by CYP3A inhibition described in the package inserts based on information in the drug list, and to clarify the status and issues.Methods: The package inserts of 24 substrate drugs of CYP3A with contraindications for itraconazole, a strong CYP3A inhibitor, were examined, and the descriptions of strong, moderate, and other CYP3A inhibitors were studied.Results: The frequencies of contraindication for strong CYP3A inhibitors were cobicistat (75%), grapefruit juice (0%), ritonavir (92%), voriconazole (67%), clarithromycin (50%), ceritinib (0%), and posaconazole (33%). On the other hand, some CYP3A substrate drugs was contraindicated with moderate CYP3A inhibitors but not with these strong CYP3A inhibitors. Furthermore, 19 CYP3A inhibitors, which were not on the drug list published in 2021, were identified as contraindications for co-administration. Majority of these were protease inhibitors, and some have been discontinued or not available in Japan.Conclusion: The findings of this study imply the necessity of organizing scientific description based on the GL strength classification. Moreover, it is important to disseminate the information and precautions for drug interactions provided in the package inserts to medical practice.

Pharmacokinetic study about compatibility of Eucommia ulmoides and Psoralea corylifolia / 中草药·英文版

OBJECTIVE@#The compatibility of Eucommia ulmoides (Eu) and Psoralea corylifolia (Pc) on the pharmacokinetic (PK) properties in the rat was explored in this study.@*METHODS@#Eu extract, Pc extract and the combined extracts (crude drug ratio was 2:1) was administered by gavage, respectively. Two PK experiments were conducted. In first one, the blood samples were collected via the occuli chorioideae vein to get the PK properties of the components. In second one, the blood samples were simultaneously collected via the internal jugular vein or portal vein at different time points and the concentrations of target ingredients were detected by LC/MS/MS to clear the location where the interaction of Eu and Pc took place in vivo.@*RESULTS@#Eight of 11 ingredients in Eu and Pc extract were determined in rat plasma. The exposure levels of geniposidic acid (GPA), aucubin (AU), geniposide (GP), pinoresinol diglucoside (PDG), psoralen glycosides (PLG) and isopsoralen glycosides (IPLG) were decreased 1/5-2/3 after administration of combined extracts. Comparing to the combined administration, the exposure of GPA and AU in plasma of single Eu administration collected via the portal vein were decreased 1/3-2/3, and the values of AUC0-24h and AUC0-∞ of GP collected from the portal vein or internal jugular vein were double increased. The other components' parameters were not significantly changed.@*CONCLUSION@#In summary, the Pc and Eu combined administration could affect the exposure of the main components of Eu extract in rats due to the changed intestinal absorption. The research on the compatibility of Pc and Eu was helpful to guide the clinical administration of Eu and Pc simultaneously.

Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling

Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.

Analysis of reported adverse liver reactions associated with drugs used to treat patients with coronavirus disease 2019

Abstract Hepatic injury has been documented in patients with coronavirus disease 2019 (COVID-19). However, pharmacotherapy can frequently impact liver alterations, given the known hepatotoxic potential of drugs not effective to treat COVID-19. The objective of the present study was to evaluate reports of suspected liver reactions to drugs used for treating COVID-19, compare their use for other indications among patients with COVID-19, and assess possible interactions between them. We obtained reports on drugs used to treat COVID-19 (tocilizumab, remdesivir, hydroxychloroquine, and/or lopinavir/ritonavir), registered on June 30, 2020, from the Food and Drug Administration Adverse Event Reporting System (FAERS) Public Dashboard. We then analyzed the risk of developing liver events with these drugs by calculating the reported odds ratios (ROR). We identified 662, 744, and 1381 reports related to tocilizumab, lopinavir/ ritonavir, and hydroxychloroquine use, respectively. The RORs (95% confidence intervals) were 6.32 (5.28-7.56), 6.12 (5.22-7.17), and 9.07 (8.00-10.29), respectively, demonstrating an increased risk of liver events among patients with COVID-19 when compared with uninfected patients. The elevated risk of reporting adverse liver events in patients with COVID-19 who receive these drugs, alone or in combination, highlights the need for careful drug selection and efforts to reduce drug combinations without notable benefits. Similar to any other condition, the use of drugs without established efficacy should be avoided.

Intrapatient variability of tacrolimus trough concentrations and its effect on serum creatinine level in kidney transplant recipients treated with nematvir/ritonavir / 器官移植

Objective To investigate the intra-patient variability (IPV) of tacrolimus trough concentrations and its effect on serum creatinine (Scr) level in kidney transplant recipients treated with nematvir/ritonavir. Methods Clinical data of 41 kidney transplant recipients infected by SARS-CoV-2 and treated with nematvir/ritonavir were collected. The usage of nematvir/ritonavir and tacrolimus was summarized. The distribution of tacrolimus trough concentrations and the attainment rate of target concentration were analyzed. The correlation between the IPV distribution of tacrolimus trough concentrations and the changes of Scr level was determined. Results Among 41 kidney transplant recipients, 46%(19/41) were given with full- and low-dose nematvir/ritonavir, and 7%(3/41) were given with high-dose nematvir/ritonavir. Use of tacrolimus was discontinued at 24 h before nematvir/ritonavir treatment in 95%(39/41) patients, and at 24 h after use of nematvir/ritonavir in 5%(2/41) patients. Tacrolimus was given at least 3 d after the 5-d course of nematvir/ritonavir in all patients. The attainment rate of tacrolimus trough concentration was 73%(30/41), 30%(3/10), 48%(15/31), 35%(11/31) and 53%(16/30) before, during, 1 week, 2 weeks and 1 month after use of nematvir/ritonavir, respectively. The median IPV was 35%(23%, 51%). Spearman correlation analysis showed that the increase of Scr level was positively correlated with IPV (rs=0.400 7, P=0.028 2). Conclusions The attainment rate of tacrolimus trough concentration is declined in kidney transplant recipients treated with nematvir/ritonavir. The IPV of tacrolimus trough concentrations is elevated. The recipients with higher IPV are prone to an elevation in Scr level.

Research progress in pharmacokinetics/pharmacodynamics and drug use of meropenem in special population / 中国药房

Meropenem is the first choice for the treatment of multi-drug-resistant bacterial infections， which has been widely used in clinical practice. However， the physiological and pathological characteristics of special populations have a significant impact on the pharmacokinetics/pharmacodynamics （PK/PD） parameters of meropenem， so it is necessary to develop individualized drug administration plan according to the characteristics of patients in clinical application. Therefore， this paper summarizes PK/PD characteristics and application of meropenem in special population， and recommends the dosage of meropenem as follows： 10-40 mg/kg， q8 h for children； 1 g， q8-12 h for elderly patients； 0.75 g， q8 h for the patients with renal insufficiency who received continuous veno-venous hemofiltration and continuous veno-venous hemodialysis； 1 g， q8 h prolonged infusion until 3 hours or 2 g， q8 h for patients with hyperrenal function； 1 g， q8 h after 2 g loading dose for patients with cirrhosis.

Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients

The liver plays a central role in the pharmacokinetics of drugs through drug metabolizing enzymes and transporters. Non-alcoholic steatohepatitis (NASH) causes disease-specific alterations to the absorption, distribution, metabolism, and excretion (ADME) processes, including a decrease in protein expression of basolateral uptake transporters, an increase in efflux transporters, and modifications to enzyme activity. This can result in increased drug exposure and adverse drug reactions (ADRs). Our goal was to predict drugs that pose increased risks for ADRs in NASH patients. Bibliographic research identified 71 drugs with reported ADRs in patients with liver disease, mainly non-alcoholic fatty liver disease (NAFLD), 54 of which are known substrates of transporters and/or metabolizing enzymes. Since NASH is the progressive form of NAFLD but is most frequently undiagnosed, we identified other drugs at risk based on NASH-specific alterations to ADME processes. Here, we present another list of 71 drugs at risk of pharmacokinetic disruption in NASH, based on their transport and/or metabolism processes. It encompasses drugs from various pharmacological classes for which ADRs may occur when used in NASH patients, especially when eliminated through multiple pathways altered by the disease. Therefore, these results may inform clinicians regarding the selection of drugs for use in NASH patients.

Application of Physiologically Based Pharmacokinetic Modeling of Lamotrigine Using PK-Sim in Predicting the Impact of Drug Interactions and Dosage Adjustment

Objectives To build a lamotrigine (LTG) physiologically based pharmacokinetic (PBPK) model (LTG PBPK) and compare it to the clinical data from South Asian Indian patients and use this model to understand the drug interactions of LTG and explore the optimal doses. Methods and Material The PBPK model was developed using the PK-Sim software platform and qualified with LTG plasma concentration data from an Indian study. The European population database was chosen as the patient setting in the software. Physiochemical data of LTG and enzyme kinetic data were incorporated from the literature. Dosing protocols were as per the previous study. Interaction models for drug interactions with carbamazepine and valproate were also simulated. Results Most of the model predicted concentration-time profiles of LTG at steady-state were well within the observed concentrations. The developed models were suitably qualified. The drug interaction model was used to assess the impact of induction and inhibition of the pharmacokinetic profile of LTG. Conclusions The predicted plasma concentrations of the developed PBPK models using the European population database were very similar to the data from Indian patients. The developed LTG PBPK models are applicable in predicting the impact of drug interactions and can yield appropriate LTG doses to be administered.

Quality control and drug-drug interactions between commercially available Metoprolol and Glimepiride tablets

Abstract Quality is paramount and needs to be maintained throughout the shelf life of pharmaceuticals. The current study aimed to evaluate the quality, potency, and drug-drug interaction in an in vivo animal model by using two drugs, namely, metoprolol and glimepiride. Tablets were selected for their physical characteristics, such as shape, size, and color. Quality control tests, such as weight variation, hardness, friability, and disintegration tests, and invitro drug release studies were performed as per USP. Drug-drug interaction and in vivo studies were carried out according to the standard protocol of the animal ethics committee. Quality control tests of both the tablets were within the specified range. The cumulative release percentages of the drugs were 81.12% and 85.36% for Metoprolol Tartrate and Glimepiride, respectively, in a physiological buffer solution within 1 h. The combination of metoprolol and Glimepiride also significantly decreased the blood glucose level in diabetic animals. However, the blood glucose level increased in the group receiving metoprolol only, but the difference was not significant. The result suggested that the formulations are safe. However, the chronic use of this combination requires frequent monitoring of blood glucose level to improve its efficacy and for the patient's safety.

Analysis of potential drug interactions in medical clinic sector in a Hospital of João Pessoa - PB

Abstract The objective of this study was to evaluate drug interactions based on medical records of patients hospitalized in University Hospital Lauro Wanderley (UHLW) in João Pessoa-PB, Brazil. This was a quantitative, descriptive study with a cross-sectional design. This research was conducted in the medical clinic of the above hospital by analyzing pharmaceutical intervention in medical records. The investigated samples consisted of all medical profiles with drug interaction information of patients hospitalized from June 2016 to June 2017. Most of these drug interactions were determined and classified by Micromedex® Solutions database. This research was approved by the Ethics Committee in Institutional Human Research, protocol number 2.460.206. In total, 331 drug interactions were found in 131 medical profiles. Dipyrone, enoxaparin, sertraline, ondansetron, quetiapine, tramadol, bromopride, amitriptyline, and simvastatin were medications that showed highest interactions. According to Anatomical Therapy Classification (ATC), drugs that act on the central nervous system result in more interactions. The most prevalent interaction was between dipyrone and enoxaparin. Some limitations of this study are the lack of notifications and data on drug interactions.

Identification and characterisation of potential drug interaction in a Hospital in Jundiai, Sao Paulo State

Abstract To identify and characterize the most frequent Drug Interaction (DI) in a Jundiaí Hospital. Exploratory, descriptive, and analytical cross-sectional study with a quantitative approach. The source of the study is 100 prescriptions made by the medical service of a hospital in Jundiaí, dispensed from August to October 2018, by the pharmacy of the mentioned hospital for palliative care, mental health, and emergency care. Data plotting in Excel. Of the 100 prescriptions analyzed 60 had at least one type of interaction, 164 DI were found, 14.6% severe, 67.7% moderate, 17.1% minor and 0.6% unspecified. The mechanism of interaction that most appeared in the study was pharmacodynamics, 54.3%, pharmacokinetics were present in 34.1% of DI and 11.6% were not specified. The group most affected by DI was male 33% of prescriptions, female 27%, and 40% showed no interactions. The age group with the most interactions was from 50 to 59 years old. Of the prescriptions that had MI, those with 4 or more interactions were the ones that prevailed. The class of drugs that presented the most interactions was psychotropic drugs. A relevant frequency of interactions was identified by the present study, being the class of psychotropic drugs the most evident and interactions of medium severity the most found, which may be responsible for lowering the clinical condition of patients and the need of possible additional interventions. The data presented may contribute as epidemiological indicators, guiding corrective actions, aiming at the welfare of patients

Influence of traditional Chinese medicines on the in vivo metabolism of lopinavir/ritonavir based on UHPLC-MS/MS analysis / 药物分析学报

A fast,reliable,and cost-effective liquid chromatography-tandem mass spectrometry method was established to determine the effects of the traditional Chinese medicine employed to treat coronavirus disease 2019,namely,Lianhua Qingwen granules,Huoxiang Zhengqi capsules,Jinhua Qinggan granules,Shufeng Jiedu capsules,and Angong Niuhuang pills,on the pharmacokinetics of lopinavir/ritonavir in rats.Blood samples were prepared using the protein precipitation method and atazanavir was selected as the internal standard(IS).Separation was performed on an Agilent ZORBAX eclipse plus C18(2.1 mm x 50 mm,1.8 μm)column using acetonitrile and water containing 0.1％formic acid as the mobile phase for gradient elution.The flow rate was 0.4 mL/min and the injection volume was 2 μL Agilent Jet Stream electrospray ionization was used for mass spectrometry detection under positive ion multiple reaction monitoring mode at a transition of m/z 629.3→447.3 for lopinavir,m/z 721.3→296.1 for rito-navir,and m/z 705.4→168.1 for the IS.The method showed good linearity in the concentration range of 25-2500 ng/mL(r=0.9981)for lopinavir and 5-500 ng/mL(r=0.9984)for ritonavir.The intra-day and inter-day precision and accuracy were both within±15％.Items,such as dilution reliability and residual effect,were also within the acceptable limits.The method was used to determine the effects of five types of traditional Chinese medicines on the pharmacokinetics of lopinavir/ritonavir in rats.The pharmaco-kinetic results showed that the half-life of ritonavir in the groups administered Lianhua Qingwen granules and Huoxiang Zhengqi capsules combined with lopinavir/ritonavir was prolonged by approx-imately 1.5-to 2-fold relative to that in the control group.Similarly,the pharmacokinetic parameters of lopinavir were altered.Overall,the results of this study offer important theoretical parameters for the effective clinical use of five types of traditional Chinese medicines combined with lopinavir/ritonavir to reduce the occurrence of clinical adverse reactions.

Analysis of interactions of immune checkpoint inhibitors with antibiotics in cancer therapy / 医学前沿

The discovery of immune checkpoint inhibitors, such as PD-1/PD-L1 and CTLA-4, has played an important role in the development of cancer immunotherapy. However, immune-related adverse events often occur because of the enhanced immune response enabled by these agents. Antibiotics are widely applied in clinical treatment, and they are inevitably used in combination with immune checkpoint inhibitors. Clinical practice has revealed that antibiotics can weaken the therapeutic response to immune checkpoint inhibitors. Studies have shown that the gut microbiota is essential for the interaction between immune checkpoint inhibitors and antibiotics, although the exact mechanisms remain unclear. This review focuses on the interactions between immune checkpoint inhibitors and antibiotics, with an in-depth discussion about the mechanisms and therapeutic potential of modulating gut microbiota, as well as other new combination strategies.

Mechanistic understanding of the inhibitory effect of cytochrome P450 3A4 and 3A5 by Wuzhi tablet (Schisandra sphenanthera extract) / 药学学报

Wuzhi tablet (WZ) is a prescribed herbal medicine extracted from Schisandra sphenanthera, which is widely used to protect the liver injury and drug-induced hepatotoxicity in clinical practices. Previous studies showed that WZ significantly increased the blood concentrations of tacrolimus, cyclosporine A, paclitaxel by inhibiting the cytochrome P450 3A (CYP3A)-mediated metabolism. CYP3A4 and CYP3A5 are the most important isoenzymes among the CYP3A subfamily. However, there are some differences in the catalytic and inhibitory activities between CYP3A4 and CYP3A5, which may lead to different risk of drug-drug and herb-drug interactions, and the risks may be further amplified in vivo. Currently, few reports have compared the herbal medicine inhibitory effects between CYP3A4 and CYP3A5 mediated metabolic reactions. Therefore, detailing the inhibitory effect of WZ on CYP3A4 and CYP3A5 will help understand and predict the potential herb-drug interaction. The results showed that WZ inhibited CYP3A4 and CYP3A5 in a NADPH-, time- and concentration- dependent manner. WZ showed more potent inhibition on CYP3A5 than CYP3A4. Cautions warranted when combining WZ with other therapeutic drugs to avoid the potential herb-drug interaction.

Pharmacokinetic study of venlafaxine combined with vinpocetine in rats / 中国药房

OBJECTIVE To study the pharm acokinetics of venlafaxine（VEN）combined with vinpocetine （VIN）in rats ，and to investigate the interaction between them. METHODS Healthy male SD rats were randomly divided into VEN group （13.5 mg/kg）， VIN group （1.8 mg/kg） and VEN + VIN group （13.5 mg/kg VEN + 1.8 mg/kg VIN ），with 6 rats in each group. Before administration，rats in each group fasted but didn ’t deprived of water for 12 hours，and were given corresponding drugs intragastrically at one time. Blood was collected from rats in each group through orbital venous plexus at different time points after administration. After plasma sample was pretreated （domperidone as internal standard ），LC-MS/MS method was adopted to determine the concentration of VEN ，active metabolite O-desmethylvenlafaxine of VEN （ODV）and active metabolite apovinblastic acid of VIN （AVA）in plasma. DAS 2.0 software was used to calculate and compare the pharmacokinetic parameters of VEN ，ODV and AVA. RESULTS Compared with VEN group ，the pharmacokinetic parameters cmax，AUC0－t，AUC0－∞，MRT0－t（except for VEN），MRT0－∞（except for VEN ）of VEN and ODV in VEN+VIN group were increased significantly ，while CL/ F and Vz/F were decreased significantly （P＜0.05 or P＜0.01）. Compared with VIN group ，there was no statistical difference in the pharmacokinetic parameters of AVA in rat plasma of VEN+VIN group （P＞0.05）. CONCLUSIONS After the combination of VEN and VIN ，VIN can affect the metabolism of VEN by increasing the absorption of VEN and ODV and slowing down their elimination.

Interaction between cyclosporine A and voriconazole in patients with allogeneic hematopoietic stem cell transplantation / 药学实践杂志

Objective To analyze the drug-drug interaction (DDI) between intravenous voriconazole (VRZ) and intravenous cyclosporine (CsA) in patients after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and provide an individualized and accurate clinical drug delivery. Methods In a self-contrast study, Allo-HSCT patients from January 2019 to December 2019 were enrolled according to the inclusion and exclusion criteria. These patients were treated with CsA and VRZ successively and the blood concentration of CsA and VRZ before and after 5-7 days of VRZ administration were determined with LC-MS/MS. The correlation between the concentration of VRZ and concentration/dose (C/D) ratio of CsA was analyzed with SPSS20.0. Results A total of 15 patients with ALLo-HSCT were enrolled. Wilcoxon sign rank sum test was used to compare the change of median C/D of CsA before and after VRZ administration, which had shown significant difference (P<0.001). Spearman correlation analysis was conducted on the increase of C/D ratio between VRZ and CsA, which had no significant correlation between them (ρ=−0.273, P=0.32). Conclusions There was obvious drug-drug interaction (DDI) between CsA and VRZ. VRZ increased CsA blood concentration significantly, but there was no significant correlation between VRZ blood concentration and the degree of concentration increase, which might be related to individual difference.

Review of the in vitro inhibitory effects of traditional Chinese medicine and its components on CYP450 enzymes in liver microsomes / 药学学报

Cytochrome P450s (CYP450) is a superfamily of phase I metabolic enzymes, which participates in more than 90% of drug oxidation. The induction or inhibition of CYP450s is the main mechanism of drug-drug interaction. In recent years, in vitro metabolism studies conducted through isolated organs, cells, or enzyme systems have developed rapidly, due to their precision and simplicity. Therefore, profiles of the in vitro metabolism studies of traditional Chinese medicines can infer the possible metabolic pathways of drugs, predict the potential drug interactions, and may enhance the rational use of drugs in clinic. This article reviews the in vitro inhibitory effects of traditional Chinese medicine, ingredients, and extracts on the activities of CYP450 enzymes in the liver microsomes, which can provide a reference for further researches on the interaction between Chinese medicine and chemical medicine.

Drug - Drug Interactions among Chronic Kidney Disease patients in a tertiary hospital.

Background: Drug interaction (more precisely ‘drug-drug interaction’) refers to modifying the action of one drug by another when administered simultaneously or in quick succession. Chronic Kidney Disease (CKD) patients often require polypharmacy, which puts them at the risk of the developing Drug - Drug Interactions (DDIs) and various adverse reactions. Not all patients taking interacting drugs experience adverse consequences, but it is advisable to take due precautions to avoid mishaps in all cases where interactions are possible. Hence, this study was undertaken to identify the DDIs among the drugs prescribed to CKD patients. Materials and methods: A Cross-sectional study was conducted in the Department of Nephrology. A total of 80 patients with CKD were included. Patients with CKD with other comorbid conditions, CKD patients of either sex above the age group of 18 years were included. LEXICOMP drug interaction software was used for potential DDI (pDDI) identification. Results: Patients mean age was 47.24±14.37 years with male predominance of 72.5 %. A total of 604 drugs were prescribed with a mean of 7.55 ± 2.73. The most common medications prescribed was Amlodipine (6.3%). DDIs were identified in 74 patients. 46 showed 1 to 5 pDDIs, 22 patients showed 6 to 10 p DDIs, 4 patients showed 11 - 15 DDIs, and 2 patients showed 16 to 20 pDDIs. According to the Lexicomp severity classification, 270 were Type C, 57 were Type D & 55 were Type B. Conclusion: The recognition of potential DDI and key combinations of drugs avoids treatment failure situations or minimizes drug toxicity .