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.

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.

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.

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.

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.

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.

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 .

Assessment of Potential Drug - Drug Interaction among the Patients Receiving Cancer Chemotherapy: A Cross-sectional Study

Objectives: To identify and assess the various potential drug-drug interactions (pDDIs) among the patients receiving cancer chemotherapy, using the database from Lexicomp® Solutions with the ultimate goal of raising awareness among clinicians for safe medication usage. Materials and Methods: It is a prospective, cross-sectional study engaged at a tertiary care hospital in South India. Data regarding clinically prescribed drugs were obtained from the patients admitted to the oncology unit of tertiary care hospital within the time frame of 6 months (June 2018 to December 2018). Frequency and clinical relevance, the onset, and Severity of pDDIs were assessed using the database from Lexicomp® Solutions version 4.1.2. Data were analyzed using the descriptive statistics. Statistical significance was analyzed using the Mann–Whitney andChi-square tests. Pearson’s correlation coefficient was used to identify the correlation between the incidence of drug-drug interactions with age, the number of drugs prescribed, and the type of cancer. Results: A total of 895 pDDIs were seen, including 261 with chemotherapeutic drugs and 634 with supportive medication. It was observed that around 14.18% of cyclophosphamide showing interaction with Ondansetron among chemotherapeutic drugs, whereas 9.14% of lithium presenting interaction with Ondansetron among supportive therapy. A statistically significant higher interaction was noted among supportive medications provided when compared to anticancer drugs (P = 0.001). Conclusions: The majority of pDDIs observed among the patients receiving chemotherapy with supportive medications as compared to anticancer chemotherapy. There is an urgent need for special safety measures to monitor and prevent drug interactions in the oncology unit.

Targeting uptake transporters for cancer imaging and treatment

Cancer cells reprogram their gene expression to promote growth, survival, proliferation, and invasiveness. The unique expression of certain uptake transporters in cancers and their innate function to concentrate small molecular substrates in cells make them ideal targets for selective delivering imaging and therapeutic agents into cancer cells. In this review, we focus on several solute carrier (SLC) transporters known to be involved in transporting clinically used radiopharmaceutical agents into cancer cells, including the sodium/iodine symporter (NIS), norepinephrine transporter (NET), glucose transporter 1 (GLUT1), and monocarboxylate transporters (MCTs). The molecular and functional characteristics of these transporters are reviewed with special emphasis on their specific expressions in cancers and interaction with imaging or theranostic agents [., I-123, I-131, I-iobenguane (mIBG), F-fluorodeoxyglucose (F-FDG) and C pyruvate]. Current clinical applications and research areas of these transporters in cancer diagnosis and treatment are discussed. Finally, we offer our views on emerging opportunities and challenges in targeting transporters for cancer imaging and treatment. By analyzing the few clinically successful examples, we hope much interest can be garnered in cancer research towards uptake transporters and their potential applications in cancer diagnosis and treatment.

Effect of Flavonoid and Triterpenoid Compounds on the Function of Organic Anion Transporting Polypeptide 1B3 / 中国药学杂志

OBJECTIVEP: To investigate the effect of flavonoids and triterpenoids on the function of organic anion transporting polypeptide 1B3. METHODS: Natural products such as flavonoids and triterpenoids are widely present in traditional Chinese medicine and daily diets. In the present study, CHO cells stably expressing OATP1B3 and its fluorescent substrate fluorescein methotrexate were employed to investigate the effect of 21 natural products on the function of OATP1B3. RESULTS: Mulberrin, glycyrrhetinic acid, glycyrrhizic acid, quercitrin, quercetin, and chrysanthemum stem-leaf flavonoids showed significant inhibitory effects on OATP1B3-mediated uptake of fluorescein methotrexate, with IC50 values being of 3.6, 3.8, 7.5, 9.0, 10.1 μmol•L-1, and 4.1 μg•mL-1, respectively. The IC50 value of glycyrrhetinic acid on OATP1B3 was comparable to its blood concentration in clinics, indicating an OATP1B3-mediated drug-drug interaction could occur. CONCLUSION: Some flavonoids and triterpenoids are OATP1B3 inhibitors. When patients take medications of OATP1B3 substrates, care should be taken to avoid coadmistration of drugs or food containing these inhibitors to circumvent the occurrence of adverse drug interactions.

Current development of physiologically based pharmacokinetic model and its application in drug clinical study / 中国临床药理学与治疗学

The physiologically based pharmacokinetic (PBPK) model, as a physiological mechanism-based model, can simulate the absorption, distribution, metabolism and excretion of drugs in the body. In recent years, it has been widely used in drug-drug interaction study, special population extrapolation, clinical trial dose selection, individualized medication and impact of different factors on the pharmacokinetic course. This review briefly describes the history and current development of PBPK model, introduces the work flow of PBPK model, and reviews its application in drug clinical study in recent years. We hope this review could provide a reference for researchers who are interested in this field.

Evaluation of the effects of resveratrol on the activity human cytochrome P450 through combined probe method / 中国临床药理学与治疗学

AIM: To evaluate the effects of resveratrol on five human cytochrome enzyme P450 subtypes, i.e. CYP1A2, CYP2D6, CYP2C9, CYP3A4, and CYP2C19, through a combined probe method. METHODS: We conducted a randomized controlled study in which 26 healthy male volunteers were recruited and were randomized into the resveratrol group and the placebo group. Volunteers were given oral placebo /resveratrol at a dose of 1 g each time, once daily for 14 days. Then, they took five oral probe drugs, caffeine (for CYP1A2), losartan (for CYP2D6), omeprazole (for CYP2C19), dextromethorphan (for CYP2C9), and midazolam (for CYP3A4). Blood samples at different times were collected to detect the concentration of the three probes, i.e. midazolam, caffeine and omeprazole; 0-8 h urine samples were collected to measure the metabolic rate of losartan and dextromethorphan. RESULTS:Compared with the placebo group, the AUC0-12, AUC0-∞, Cmax of caffeine in the resveratrol group was increased by 32.10% (P0.05) as compared with the placebo group. The 8 h urinary DTM/DT ratio was increased by 79.91% (P=0.003) and 8 h urinary losartan/E-3174 ratio was increased by 531.34% (P<0.001).CONCLUSION: Resveratrol significantly inhibited the enzymatic activities of CYP1A2, CYP2D6 and CYP2C9 after repeated administration, but did not significantly change the enzymatic activities of CYP3A4 and CYP2C19.

Assessment of drug-drug interactions in the prescription of elderly patients on cardiovascular drugs

Background: Cardiovascular disease is one of the major causes of mortality and morbidity in a developing country like India. These patient’s prescription contains multiple drugs to reduce the mortality and morbidity and they also contain drugs for treatment of co morbidities leading to polypharmacy. The main objective of the study was to identify the pattern of drug- drug interaction (DDI) in patients on cardiovascular drugs with various co existing morbidities.Methods: This study was conducted in the Department of General Medicine of a tertiary care center. Prescription of 200 patients were analysed for demographic details like gender, age, comorbidities and drugs prescribed. DDI were assessed using Micromedex software.Results: In this study, conducted on the prescription of 200 elderly patients, 13 (66%) prescription had 408 DDI, of which 158 (39%) were major, 246 (60%) were moderate and 1 (0.02%) was contraindicated and 3 (0.007%) were minor.Conclusions: It can be concluded from the present study that the risk of DDI increases with the increase in number of drugs in the prescription and there is increase in number of drugs in the prescription with the increase in number of co morbidities. The antiplatelet and anticoagulant group of drugs were responsible for majority of DDI, followed by antihypertensives and hypoglycaemic agents. Most of these DDI could be avoided with slight modification in the dosage regimen based on the pharmacokinetics and pharmacodynamics of the drug.

Pharmacokinetics and sedation of sufentanil and dexmedetomidine combination in rats / 中国药理学与毒理学杂志

OBJECTIVE To evaluate plasma pharmacokinetics, distribution of target organs, sedative effect and respiratory depression of sufentanil (SFTN), and dexmedetomidine (DEM) in rats, and to explore the potential drug-drug interactions between the two drugs. METHODS  Rats were intravenously injected with SFTN 20.0 μg•kg-1, DEM 25.2 μg•kg-1 and SFTN+DEM (SFTN 20.0 μg•kg-1, DEM 25.2 μg•kg-1), respectively. Plasma samples were taken at different time points (2, 5, 15, 30 min and 1, 2, 4, 6, 8 h) to determine the concentrations of SFTN and DEM using the liquid chromatography-mass spectrometry (LC-MS/MS) quantitative method established in this study. The same method was used to determine the concentrations of SFTN and DEM in plasma and brain samples taken at different time points (5, 15, 30, 60 and 120 min). Pharmacokinetic parameters were obtained by noncompartmental analysis performed using Phoenix WinNonlin 7.0 (Pharsight, California). The duration of drug-induced loss of right reflex (LORR) and respiratory function were also measured using instrument monitoring. RESULTS  An LC-MS/MS method for quantitative analysis of plasma SFTN and DEM was established and validated. The Cmax,;t1/2, and Cl ;of SFTN in SFTN group were (22.2±2.6) ug•L-1, (2.13±0.69) h and (2288±446) mL•h-1•kg-1, respectively, compared with (15.9±9.4) μg•L-1, (1.22±0.13) h and (3565±743) mL•h-1 •kg-1 in SFTN+DEM group. The Cmax, t1/2, and Cl of DEM in DEM group were (14.0±8.9) μg•L-1, (1.21±0.15) h and (4235±752) mL•h-1•kg-1, compared with (9.4±3.5) μg•L-1, (1.08±0.26) h and (4796±744) mL•h-1•kg-1 in SFTN+DEM group. The Cmax ratio of SFTN in brain and plasma of SFTN+DEM group was 0.49, which was 1.3-fold that of SFTN group (0.45). The Cmax ratio of DEM in brain and plasma of SFTN + DEM group was 16.9, which was 12-fold that of DEM group (1.42). The duration of LORR of SFTN, DEM, and SFTN+DEM groups was 370±13, 41±5 and (104±24) min, respectively, and that of SFTN+DEM group was more significantly extended than those in SFTN and DEM groups (P<0.01). Respiratory depression of SFTN+DEM group was not further aggravated compared with SFTN group, but the duration of inhibition was extended (P<0.05, P<0.01). CONCLUSION  The combination of SFTN and DEM can cause drug-drug interactions, which may promote the sedation and prolong the respiratory depression by increasing the exposure level of DEM brain tissue. In clinical application, attention should be paid to the possible drug-drug interactions or adverse reactions caused by the combination of these two drugs.

Potential drug-drug interactions among medications prescribed to adult Filipinos at a primary care clinic in a government teaching hospital

Background@#A drug-drug interaction (DDI) is a pharmacologic or clinical response to the administration of a drug that can result in adverse outcomes. DDIs are considered preventable adverse drug reactions because these interactions can be learned, predicted and recognized. @*Objective@#To determine potential drug-drug interactions (pDDI) among medications prescribed to adult patients consulting at a primary care clinic in a government teaching hospital. @*Methods@#This was a 6-month retrospective cross-sectional study of drug prescriptions based on medical records of adult Filipinos who were seen and managed at a primary care clinic in a government teaching hospital. Medical charts were systematically selected based on a sampling frame with inclusion and exclusion criteria.@*Results@#A total of 1,490 medical records of adult Filipino patients were included in the study. There were a total of 261 unique prescriptions based on generic formulations and an overall total of 5,978 drugs for a 6-month period of clinic consultations. An average of 4 medications (SD±1.63) were prescribed for every consultation recorded in the medical chart. From the charts that were reviewed, 23% of all adults were given a prescription of 4 drugs (N=348/1490), 26% had 3 drug prescriptions (N=386/1490) and 18% had two drugs, respectively, per clinic visit. Overall, 714/9054 (7.88%) medication pairs were seen to have potential drug interactions. The top three most common drug pairs with pDDI were amlodipine-simvastatin, losartan/hydrochlorothiazide-metformin and aspirin-furosemide. Five hundred twenty-five drug pairs had pharmacodynamic interactions (525/714) while 94 drug pairs (15%) had pharmacokinetic interactions. @*Conclusion@#Potential drug-drug interactions were observed in 8% of medications prescribed to adult Filipinos seen at Family Medicine Clinic in a government hospital. Seventy-four percent (74%) of the drug pairs with pDDIs were pharmacodynamic and 15% were pharmacokinetic interactions.

Characteristics of chronic hepatitis C in the elderly and the progress of antiviral therapy / 中华临床感染病杂志

Elderly patients have become a special concern in the management of hepatitis C .Their HCV exposure time is long and the risk of liver disease and extrahepatic complications is high .With the advent of direct antiviral drugs (DAA), the treatment of chronic hepatitis C has been significantly improved , and the cure rate of virology can be more than 90% in the elderly patients , with a high safety.However, elderly patients often have more underlying diseases and the drug use will be more complicated , resulting in drug interaction ( DDI) and increasing the challenge of treatment management.This article reviews the requirements for comprehensive evaluation of elderly patients before DAA treatment , including liver and kidney function, combined drug use and potential DDI.The monitoring of adverse events and DDI , and the countermeasures are also discussed in the article.

A prospective observational study to evaluate potential drug-drug interactions in patients admitted in intensive care unit, at BRIMS tertiary care hospital in Bidar, India

Background: Drug interaction occurs when presence of one drug affects the activity of another when, both are co-administered. 6-30% of adverse events (AEs) with significant hospitalizations or death are by drug-drug interactions(DDI). There is increased possibility to prevent the potential drug-drug interactions (pDDIs), if their prevalence and pattern are determined accurately before their occurrence. Hence this study aimed to evaluate the prevalence of pDDIs in ICU patients at BRIMS tertiary care hospital, Bidar.Methods: This prospective observational study included 30 patients admitted in ICU of BRIMS hospital for >24hrs of either gender, aged >18yrs. The study was conducted for a period of 3 months. Data was collected from the case records of patients on the predesigned proforma. Potential drug-drug interactions were classified based on their severity and the risk of Potential drug-drug interactions was estimated by Lexicomp, inc.version; 3.0.1.drug interact android mobile application.Results: Out of 35 patients admitted in the ICU, 30 cases were included in the study. The mean age of study population was 56.3years. The study population was exposed to a total of 330 medicines during the hospital stay with an average of 11.7 drugs per patient. The prevalence of pDDI was 93.3% (28) with an average of 9.75 pDDI per patient. According to Lexicomp drug interact android mobile application majority (63%) of pDDI were found to be moderate in their severity, 67% belonged to type C risk.Conclusions: The study showed higher prevalence of pDDI among ICU patients due to the complexity of the pharmacotherapies administered.

Effects of schisandrin B on pharmacokinetics of doxorubicin in rats / 中国药科大学学报

@#To investigate the effect of combination of schisandrin B and doxorubicin on the pharmacokinetic behavior of doxorubicin in SD rats. An LC-MS/MS method was established for the determination of doxorubicin and its main metabolite doxorubicinol in SD rats plasma. Separation was performed on Agilent Eclipse XDB-C18 column(100 mm×2. 1 mm, 3. 5 μm)using 0. 1% formic acid solution and acetonitrile as mobile phase with a liner gradient program. The ion transitions were performed under ESI position model at m/z 544. 2→397. 3(doxorubicin), m/z 546. 2→399. 2(doxorubicinol), m/z 528. 2→381. 2(daunorubicin, internal standard). Calibration curves of doxorubicin(0. 500-500 ng/mL)and doxorubicinol(0. 200-50. 0 ng/mL)showed good linear regression. The precision and accuracy met the requirements. The variation coefficient of extraction recovery and matrix effect was less than 15%. The AUC0-t of doxorubicin were(605. 69±145. 84)and(564. 53±23. 99)ng ·h/mL in alone and combined group, respectively. The AUC0-t of doxorubicinol were(26. 69±13. 41)and(29. 00±2. 78)ng ·h/mL, respectively. Results indicated that, schisandrin B had not affected the pharmacokinetic behavior of doxorubicin in SD rats.