ABSTRACT
Objective: In patients with specific backgrounds, comprehensive identification of health problems and proactive pharmacist intervention are crucial to providing safe and effective medical care. However, there are insufficient reports on chemotherapy regimen selection and supportive care management in patients taking immunosuppressants. In this study, to circumvent adverse events, pharmacists intervened with a patient administering tacrolimus (TAC) using known information, focusing on multiple factors attributable to the patient in addition to drug interactions.Methods: The patient was a male in their 70s who received palliative chemotherapy for gastric cancer during their dermatomyositis treatment with TAC. Pharmaceutical support for cancer chemotherapy was provided using the following four procedures: (1) Patient information was collected from interviews and electronic medical records to identify patient-specific problems; (2) Basic pharmacological information was collected from tertiary sources, focusing on the interaction between TAC and aprepitant (APR). Furthermore, clinical reports were collected, and the pharmacokinetic drug interaction significance classification system was used for quantitative predictions; (3) The information obtained in steps 1) and 2) was evaluated, and comprehensive proposals linked to the patient information were presented; (4) Adverse events, TAC blood level, and patient outcomes were monitored after treatment initiation.Results: A chemotherapy regimen consisting of S-1/oxaliplatin therapy without APR was selected. The adverse effects were controllable, and the treatment was completed without many adverse events. Meanwhile, TAC adherence was unaffected by cancer chemotherapy, and the TAC blood concentration or dose ratios were controlled within the same range as previously reported.Conclusion: In cancer chemotherapy, for cases with limited evidence or information, comprehensive pharmaceutical support was provided using known patient information, considering multiple patient factors. This report is beneficial as an example of supportive care management by a pharmacist and contributes to providing optimal service in cases with specific backgrounds.
ABSTRACT
Pregnane X receptor (PXR) is a ligand-activated nuclear receptor that transcriptionally upregulates drug-metabolizing enzymes [e.g., cytochrome P450 3A4 (CYP3A4)] and transporters. Although the regulation of PXR target genes is well-characterized, less is known about the regulation of PXR protein level. By screening an RNAi library, we identified the F-box-only protein 44 (FBXO44) as a novel E3 ligase for PXR. PXR abundance increases upon knockdown of FBXO44, and, inversely, decreases upon overexpression of FBXO44. Further analysis revealed that FBXO44 interacts with PXR, leading to its ubiquitination and proteasomal degradation, and we determined that the F-box associated domain of FBXO44 and the ligand binding domain of PXR are required for the functional interaction. In summary, FBXO44 regulates PXR protein abundance, which has downstream consequences for CYP3A4 levels and drug-drug interactions. The results of this study provide new insight into the molecular mechanisms that regulate PXR protein level and activity and suggest the importance of considering how modulating E3 ubiquitin ligase activities will affect PXR-mediated drug metabolism.
ABSTRACT
The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus (T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1, and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM. Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug-drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug-drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.
ABSTRACT
Aim: The study aimed to determine the prevalence of potential drug-drug interactions (PDDIs) and potentially inappropriate medications (PIMs) among geriatrics. Methods: A prospective observational study was conducted for six months in the Department of Geriatrics, M.S. Ramaiah Teaching Hospital, Bangalore. PDDIs and PIMS were analyzed using micromedex database and Beer's criteria respectively. Results: Among 395 prescriptions, 221(56%) prescriptions showed 559 pDDIs and 41(10.4%) PIMs. Almost 281(50.3%), 260(46.5%), 16(2.7%) and 2(0.3%) pDDIs were categorised as major, moderate, minor and contraindicated respectively. Almost 321(57.5%) were synergistic and 196(35.0%) were antagonistic drug interactions. Pearson correlation value (R) is 0.9957 which showed a strong positive correlation. Conclusion: This study created awareness on drug interactions among geriatrics and help the practitioners to prescribe drugs with a low risk of pDDIs. The authors suggest PIM monitoring in geriatrics to avoid adverse effects and improve patients' quality of life.
ABSTRACT
Background: Drug-drug interactions are quite prevalent, especially in the geriatric population with comorbidities. It affects the effectiveness, safety, and tolerability of the medications they use. Aims and Objectives: This study aims to analyze and identify potential drug-drug interactions (pDDIs) in hypertensive patients using Medscape databases. Materials and Methods: A prospective and observational study was conducted in the Hypertension clinic of KMC, Chennai, for 3 months during November 2019–January 2020. Hypertensive patients of both sexes attending hypertension clinics with an age of more than 18 years and taking more than two antihypertensive drugs were included in the study. The use of Medscape databases enabled the appropriate data to be gathered and evaluated for pDDIs. Results: Three hundred patients in all were enrolled for the trial. One hundred and forty out of the 300 patients had pDDIs. Out of 140 patients, the majority (55%) were between the ages of 40 and 60. Males (56.4%) had a higher prevalence of pDDIs than females (43.6%). Atenolol, enalapril, and furosemide were the most frequently used medications in the present study that caused pDDIs, accounting for 29.8%, 19.5%, and 18.6%, respectively. Conclusion: The prevalence of pDDIs was found to be 46.6% overall, and an increase in comorbidities and polypharmacy were revealed to be important risk factors for the emergence of several pDDIs. Most of the antihypertensives were shown to interact frequently with calcium carbonate.
ABSTRACT
Objetivo Identificar los predictores clínicos y farmacoterapéuticos asociados a los niveles de severidad de las reacciones adversas (RAM) e interacciones medicamentosas (IM) en pacientes hospitalizados post accidente cerebrovascular. Métodos Estudio analítico, predictivo y transversal mediante el modelo de regresión lineal múltiple. Los niveles de severidad de las potenciales reacciones adversas e interacciones medicamentosas se evaluaron mediante Drugs.com. Resultados De la evaluación de 992 prescripciones médicas de 55 (56,7%) pacientes mujeres y 42 (43,3%) varones post accidente cerebrovascular isquémico 62 (63,9%) y hemorrágico 35 (36,1%), se identificó un total de 11 790±46,8 potenciales reacciones adversas y 1 034±9,8 interacciones medicamentosas. La hipertensión arterial se asoció a las reacciones adversas graves y moderadas, en tanto que la neumonía intrahospitalaria y alcalosis metabólica a reacciones adversas leves y moderadas. La alcalosis metabólica se asoció a las interacciones medicamentosas moderadas y leves. Los predictores farmacoterapéuticos como la prescripción en polifarmacia y el uso de antibióticos se relacionaron con reacciones adversas graves, moderadas y leves; los antidiabéticos se relacionaron con interacciones medicamentosas graves, moderadas y los fármacos para terapia cardiaca con interacciones medicamentosas leves. Conclusiones Las variables clínicas como factores de riesgo cardiovascular, presencia de comorbilidades que exacerban las enfermedades crónicas no trasmisibles, los signos y síntomas de alarma, el mayor tiempo de estancia hospitalaria y la prescripción en polifarmacia fueron predictores de mayor frecuencia de reacciones adversas e interacciones medicamentosas graves y moderadas que requieren especial vigilancia y estudio individualizado.
Objective To identify clinical and pharmacotherapeutic predictors associated with severity levels of adverse reactions and drug-drug interactions in post-stroke hospita-lized patients. Methods Analytic, predictive, cross-sectional study using multiple linear regression modeling. Severity levels of potential adverse reactions and drug-drug interactions were assessed using Drugs.com. Results From the evaluation of 992 medical prescriptions of 55 (56.7%) female and 42 (43.3%) male patients post ischemic stroke 62(63.9%) and hemorrhagic stroke 35 (36.1%); a total of 11 790±46.8 potential adverse reactions and 1 034±9.8 drug-drug interactions were identified; arterial hypertension was associated with severe and moderate adverse reactions; while in-hospital pneumonia and metabolic alkalosis with mild and moderate adverse reactions. While metabolic alkalosis was associated with moderate and mild drug-drug interactions. Pharmacotherapeutic predictors such as polypharmacy prescription and antibiotic use were related to moderate and mild severe adverse reactions; antidiabetic drugs were related to moderate and severe drug-drug interactions and cardiac therapy drugs were related to mild drug-drug interactions. Conclusions Clinical variables such as cardiovascular risk factors, presence of comorbidities that exacerbate chronic noncommunicable diseases, alarm signs and symptoms, longer hospital stay, as well as polypharmacy prescriptions, were predictors of a higher frequency of severe and moderate adverse reactions and drug-drug interactions, which require special vigilance and individualized study.
ABSTRACT
Background: Increasing use of drugs has led to drug-drug interactions (DDIs) which necessitate their awareness among the health-care providers to reduce the hospital admissions due to their adverse drug reactions. Aim and Objectives: This study aims to assess and compare the knowledge, attitude, and practice (KAP) of DDIs among interns and nurses and to evaluate the impact of an educational program with a pre-and post-test questionnaire. Materials and Methods: An educational program about DDIs was conducted for the interns and nurses to evaluate their KAP by a pre-test and post-test pre-verified 20-point questionnaire about DDI. Results: There was a statistical significant difference (P < 0.05) in gender (females: Males = 77:16) among the interns and nurses and their mean age was 23 ± 0.87 years and 21.3 ± 0.83 years, respectively. Both the groups fared well in post-test compared to pre-test in the knowledge (questions=7), attitude (questions=5), and practice (questions=8) domain which was statistically significant. On comparing the post-test scores, both the groups showed no difference statistically (P > 0.05) in the knowledge and attitude domain, while the nurses group showed more improved mean score than interns in terms of practice of DDI. Conclusion: The educational program about DDIs was effective among the interns and nurses with regard to their KAP assessment and they equally performed well. This implies that the awareness program about DDIs was successful among the interns and nurses who form the lower strata in delivering the health-care needs to the society.
ABSTRACT
Abstract Our aim was to determine the prevalence of potential drug-drug interactions (pDDIs) and to identify relevant factors associated with the occurrence of the most dangerous or contraindicated pDDIs (pCDDIs) in hospitalized patients with spontaneous intracerebral hemorrhage (sICH). A retrospective cross-sectional study was performed enrolling all consecutive patients with sICH treated at the Neurological Intensive Care Unit, Clinical Center in Kragujevac, Serbia, during the three-year period (2012-2014). The inclusion criteria encompassed patients aged 18 years and over, those diagnosed with ICH, and those prescribed at least two drugs during hospitalization, while we did not include patients whose hospitalization lasted less than 7 days, those who were diagnosed with other neurological diseases and patients with incomplete medical files. For each day of hospitalization, the online checker Micromedex® software was used to identify pDDIs and classify them according to severity. A total of 110 participants were analysed. A high prevalence of pDDIs (98.2%) was observed. The median number of pDDIs regardless of severity, was 8.00 (IQR 4.75-13.00;1-30). The pairs of drugs involving cardiovascular medicines were the most commonly identified pDDIs. Twenty percent of the total number of participants was exposed to pCDDIs. The use of multiple drugs from different pharmacological-chemical subgroups and the prescribing of anticoagulant therapy significantly increase the chance of pCDDI (aOR with 95% CI 1.19 (1.05-1.35) and 7.40 (1.13-48.96), respectively). This study indicates a high prevalence of pDDIs and pCDDIs in patients with sICH. The use of anticoagulant therapy appears to be the only modifiable clinically relevant predictor of pCDDIs.
Subject(s)
Humans , Male , Female , Adult , Patients/classification , World Health Organization , Cerebral Hemorrhage/pathology , Drug Interactions , Intensive Care Units/classification , Pharmaceutical Preparations/analysis , Cross-Sectional Studies/methods , Hospitalization , Anticoagulants/adverse effectsABSTRACT
Abstract The aim of our study was to assess risk factors for potential drug-drug interactions (pDDIs) of statins across different phases of treatment of acute coronary syndrome (ACS) patients: from the point of first medical contact to the coronary angiography (first phase), after coronary angiography to the last day of hospitalization (second phase) and at discharge from hospital (third phase). This was a post hoc analysis of the data collected during the retrospective observational cohort study conducted at the Clinic for Cardiology of the Clinical Centre Kragujevac, Serbia. Patients prescribed statins were identified from the original study population: 156, 240 and 236 patients for the first, second and third phases, respectively. At least one statin pDDI was present in 113 (72.4%), 161 (67.1%) and 139 (58.9%) patients in the first, second and third phases, respectively. Heart failure, arrhythmias after ACS, CRP, triglycerides, length of hospitalization, number of prescribed drugs, antiarrhythmic drugs, and clopidogrel seem to increase the risk of statin pDDIs in at least one treatment phase. Physicians should be vigilant to the possibility of statin pDDIs in ACS patients who have factors that may increase their rate.
Subject(s)
Humans , Male , Female , Adult , Patients/classification , Risk Factors , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Drug Interactions , Acute Coronary Syndrome/pathology , Pharmaceutical Preparations/administration & dosage , Cardiology/classification , Coronary Angiography/instrumentation , Serbia , ClopidogrelABSTRACT
Clinically, patients with tuberculosis (TB) combined with hepatitis C virus (HCV) infection often require simultaneous treatment. Consequently, when anti-HCV and TB drugs are used in combination drug-drug interactions (DDIs), anti-TB drug-induced hepatotoxicity, and liver disease states need to be considered. This paper focuses on discussing the metabolic mechanisms of commonly used anti-TB and HCV drugs and the selection options of combined drugs, so as to provide rational drug use for TB patients combined with HCV infection.
Subject(s)
Humans , Chemical and Drug Induced Liver Injury , Coinfection/drug therapy , Hepacivirus , Hepatitis C/drug therapy , Pharmaceutical Preparations , Tuberculosis/drug therapyABSTRACT
Drug-drug interactions (DDI) of tyrosine kinase inhibitors (TKIs) mediated by metabolic enzymes and transporters have become an important issue in clinical practice recently. In addition to CYP450 enzymes, uridine diphosphate glucuronidases (UGTs) are another class of metabolic enzymes involved in the metabolism of TKIs, and most TKIs can inhibit the UGTs in vitro. Potential clinically meaningful DDIs may occur with the co-administration of TKIs and substrates or inhibitors of UGTs. This paper will mainly focus on the UGTs-mediated drug-drug and the effect of UGT1A genotype on the drug interactions of TKIs and explores strategies to address, aiming to provide clinicians and pharmacists with references for the safe and rational application of TKIs.
ABSTRACT
In order to improve the efficacy or reduce the side effects, the combination of two or more drugs is often used in clinical practice, which often brings new medication problems that change the process or efficacy of a drug in vivo due to combination. This article reviews the clinical drug-drug interaction (DDI) researches of 44 novel molecular entities which were approved to be launched in China from January 2000 to March 2021. Among them, clinical DDI trials based on test drugs as substrates of the metabolic enzymes (11/44) especially as the substrates of CYP3A4 (7/11) are dominant. The results show that most of test drugs were CYP3A4 substrates with a moderate or lower sensitivity, and no highly sensitive substrates were found. The second is the clinical DDI trials based on synergy or reducing side effects, which mainly focus on the fields of tumors, diabetes, and viral infections, and these studies have not shown pharmacokinetic interactions with clinical significance. The DDI trials of test drugs as metabolic enzyme modulators account for 7/44. And transporter-based DDI trials are relatively rare and most of them are in vitro studies. With the in-depth study of drug metabolism/transport mechanisms in vivo and in vitro, especially the development of clinical trials of radioisotope-labeled drugs and computer simulations, the overall level of DDI research in China is gradually improving, which will provide a solid scientific foundation to ensure drug safety.
ABSTRACT
Drug-drug interactions (DDI) change dose-response relationships, and may result in low efficacy or high toxicity, which are important considerations especially in medical practice with multiple-drug therapies. Predicting clinically significant drug interactions during new drug development is an important part of benefit and risk assessment in drug development and review. This article summarizes the purpose and significance of drug interactions in new drug development, the main content and precautions of DDI studies in vivo and in vitro. Drug interaction studies on novel drug approvals for 2020 in the National Medical Products Administration (NMPA) and US Food and Drug Administration (USFDA) are examined, respectively. It aims to provide reference for DDI studies and regulatory reviews in new drug development in our country.
ABSTRACT
Objective: To identify frequency, type, severity and predictors of potential drug-drug interactions(pDDIs), potential drug-food interactions(pDFIs), potential drug-alcohol interactions(pDAIs) and potential drug-tobacco interactions(pDTIs) and most frequently interacting drug combination pairs in hospitalized patients from departments(depts) of General Medicine(GM), Orthopedic(Ortho), Gynecology(OBG), Pulmonology(Pulmo), General Surgery (GS), Psychiatry (Psych), Otolaryngology(ENT) and Dermatology (Derm) of study population. Methods: A Prospective Observational Study was conducted in eight major dept's of a tertiary care teaching hospital for a period of 6 mo. A sample size of 650 prescriptions reflecting admission no's for each department were used. Results: A total of 650 patients were included in the study. Among them, 282(43.4%) were males and 368(56.6%) were females. The mean age of the study population was 39.67±15.23. A total of 487 pDDIs, 734 pDFIs, 586 pDAIs and 159 pDTIs were found out of 650 hospitalized episodes. OBG showed the highest pDDIs and pDAIs. Highest pDFIs and pDTIs were seen in Pulmo. The majority of DDIs were minor, DFIs and DAIs were moderate and DTIs were of major in severity. Pharmacokinetic types of interactions were seen in the majority of the depts. Logistic regression analysis showed that Polypharmacy was associated with the occurrence of DIs. Most of the DIs repeated several times in particular depts and a list of these combinations was prepared. Conclusion: With the high occurrence of overall DIs and characteristic patterns of DIs combination pairs among different departments of the hospital, the presence of clinical pharmacists in hospitals can play a great role, especially in developing nations like India where their role in hospitalized settings is always controversial.
ABSTRACT
Background:Statins perceived to have favorable safety profile. Although many people on statin therapy do well but no drug is without potential for side effects. Awareness about risks as well as benefits of drugs is needed particularly drugs which are used on wide scale like statins because even uncommon side effects can have significant health impact. Objectives of the Study: To determine side effects occurrence among Saudi patients taking statins and to evaluate drug-drug interactions in Saudi patients taking statins.Methodology:Self administered cross sectional study conducted during a period of four months from October 2018 to January 2019 in Turaif general hospital, Saudi Arabia on random sample of 500 Saudi patients out of which 330 participants were included in the study which were taking different types of statins medication using self-administered questionnaire in Arabic language specially designed for the research purpose after obtaining verbal consent and the data analyzed by SPSS program.Results:A total of 330 patients; 128 (39%) females and 202 (61%) males—participated in the study. The majority 165 (50%) were in the age-group of 50 –59 years. Simvastatin was the most commonly used statin among study participants 136 (41%) followed by rosuvastatin114 (35%). Among the participants, there were some patients who take drugs which have drug interactions with statins; there were 64 (19%) take Amlodipine with simvastatin, 13 (4%) and 6 (2%) take esomeprazole and ompeprazole respectively with statins. Only 9 (3%) reported that they were advised by pharmacist to avoid grape fruit. Majority of participants 309 (94%) reported neck pain, difficulty in walking, frequently fatigue after starting on statin. Also majority of participants 320 (97%) suffer from muscle pain after starting statins medications. Conclusion:The percentage of statin related side effects in this study population is high especially myopathy. Also some patients in this study taking medications that have drug interaction with statins, Counseling to patient regarding statin therapy appear to be insufficient. So, this study indicate that there's a need for more efforts from the physicians and pharmacist to avoid prescribing or dispensing medication that have drug-drug interaction with statins and provide counseling to patients regarding their statin therapy
ABSTRACT
Hospitalized patients with left ventricular failure (LVF) are at high risk for potential drug-drug interactions (pDDIs) and its related adverse effects owing to multiple risk factors such as old age, comorbidities and polypharmacy. This cross-sectional study conducted in two tertiary care hospitals aim to identify frequency, levels and predictors of pDDIs in LVF patients. Data about patients' demographic, hospital stay, medication therapy, sign/symptoms and laboratory test results were collected for 385 patients with LVF. Micromedex Drug-Reax® was used to screen patients' medication profiles for pDDIs. Overall prevalence and severity-wise prevalence of pDDIs were identified. Chi-square test was performed for comparative analysis of various variables. Logistic regression was applied to determine the odds-ratios (OR) for predictors of pDDIs. The prevalence of pDDIs was 96.4% (n=371). Overall 335 drug-interacting pairs were detected, which were presented in a total of 2870 pDDIs. Majority of pDDIs were of major- (48.9%) and moderate-severity (47.5%). Logistic regression analysis shows significant association of >6 all types of pDDIs with >12 drugs as compared with <8 drugs (OR=16.5; p=<0.001). Likewise, there was a significant association of >4 major-pDDIs with men as compared with female (OR=1.9; p=0.007) and >12 drugs as compared with <8 drugs (OR=10.9; p=<0.001). Hypotension (n=57), impaired renal function (23) and increased blood pressure (22) were the most frequent adverse outcomes associated with pDDIs. This study shows high prevalence of pDDIs in LVF patients. Majority of pDDIs were of major- and moderate-severity. Male patients and those prescribed greater number of medicines were more exposed to major-pDDIs
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Patients , Pharmaceutical Preparations/analysis , Ventricular Dysfunction, Left/pathology , Drug Interactions , Tertiary Healthcare/ethics , Demography/classification , Cross-Sectional Studies/methods , Risk Factors , Patient Safety , Heart Diseases/classification , HospitalsABSTRACT
Objective: The aim of the present study was to assess the prevalence, risk rating and the severity of hazardous pDDIs (potential drug-drug interactions) in the prescribed pharmacotherapy in the hospital discharged heart failure (HF) patients, primarily with co-administered drugs with narrow therapeutic index (statins, anticoagulants, antithrombotic drugs). Methods: The prescriptions of chronic heart failure patients for one year (January-December 2014) were analyzed for pDDIs through Lexi-interact® software. DDIs belonging to the categories D (Consider therapy modification) and X (Avoid combination) and/or severity of drug interaction-major, were selected for the study. Results: After reviewing the medical records of 985 patients, 239 patients were selected based on the criteria mentioned above. The average number of prescription drugs at hospital discharge was 7.27 medications (±1.84 SD) per patient. The total number of pDDIs was 1483 or approximately 6.2 (±3.89 SD) pDDIs per patient. With respect to the risk rating, in categories D and X were detected 76 (5.12 %) and 2 (0.13 %) pDDI, respectively. The major pDDIs were 108 (7.28 %). Conclusion: HF patients are at high risk of pDDIs. Screening of prescriptions for pDDIs and monitoring of pharmacotherapy in terms of response and associated adverse drug events will contribute to patient safety.
ABSTRACT
Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.
ABSTRACT
Objective: To evaluate the antiplasmodial activity and safety of organic and aqueous flower extracts of Chrysanthemum cinerariaefolium from Kenya, singly and in combination with chloroquine, lumefantrine and piperaquine. Methodology: Antiplasmodial activity of organic and aqueous flower extracts of C. cinerariaefolium was assessed in vitro by serial micro-dilution assay technique against Plasmodium falciparum, and in vivo using the 4-day suppressive test as well as the established infection test against P. berghei ANKA in mice. To determine the safety of the extracts, cytotoxicity evaluation of extracts against Vero E6 cells and acute toxicity studies in mice were also done. Results: In vitro antiplasmodial assays showed that methanolic extract of C. cinerariaefolium flowers was active, petroleum ether extract was moderately active, while the aqueous extract was inactive. Methanolic extract combined with chloroquine (CQ) against CQ-sensitive (3D7) and CQ-resistant (W2) P. falciparum showed marked synergy. Both methanol and aqueous extracts (1000mg/kg) showed chemosuppression of >45% (P<0.05) in both 4-day suppression test and established infection test against P. berghei ANKA in mice. Lumefantrine (LU) or piperaquine (PQ) combined with either methanol or aqueous extracts showed chemosuppression of >63% (P<0.05) against LU-resistant and PQ-resistant P. berghei ANKA strains, indicating synergistic interactions. Methanolic and aqueous flower extracts of C. cinerariaefolium had no cytotoxic effect on Vero E6 cells and no overt signs of toxicity in mice. Conclusion: The findings showed that C. cinerariaefolium flower extracts are safe in mammalian systems, have antiplasmodial activity and have potentiation effect of conventional antimalarials. There is need therefore to further explore the plant’s bioactive molecules which may serve as template for development of novel, effective and affordable antimalarial agents for management of malaria.
ABSTRACT
Tuberculosis patients with positive antibody to hepatitis C virus (TB-HCV patients) are often seen in clinical practice, and these TB-HCV patients include those with HCV infection. That makes the clinical management and diagnosis/treatment of TB-HCV difficult. This article introduces the prevalence of TB-HCV around the world, and analyzes the potential issues in the diagnosis and treatment of TB-HCV patients, such as drug-drug interactions, drug-induced liver injury, HCV reactivation, and TB reactivation. Through this review, it is recommended that the management should be strengthened and the appropriate therapeutic regimen should be selected in the diagnosis and treatment of TB-HCV patients.