Co-prescribed Drugs Research Articles

PRESCRIPTION PATTERN OF NUTRACEUTICALS IN PATIENTS VISITING A TERTIARY CARE HOSPITAL, KATHMANDU, NEPAL

Objectives: This study aims to provide a comprehensive analysis of the prescription pattern of nutraceuticals in patients visiting a tertiary care hospital in Kathmandu which includes identification of commonly prescribed nutraceuticals, analysis of co-prescribed drug classes, identification of major nutraceutical compositions, analysis of patient expenditure on nutraceuticals, and quantification of nutraceutical availability. Methods: A purposive sampling method was used to conduct a descriptive cross-sectional study involving 304 patients from the outpatient departments of a tertiary care hospital, Nepal. Data on patients’ sociodemographic characteristics, co-prescribed drugs, nutraceutical details, and supplement expenses were collected using a structured questionnaire and form. Patient cards provided the necessary information, which was then analyzed with SPSS-16 and Microsoft Excel. Results: Out of 304 prescriptions analyzed, 64% were prescribed to females and 26% to patients aged 31–45 years. The general medicine department accounted for 44% of nutraceutical prescriptions, with multivitamins being the most common (91%). Tablets were the preferred dosage form 56%, and gastrointestinal disorder medicine was commonly co-prescribed with nutraceuticals. Nutraceuticals alone accounted for approximately 52% of the total medicine cost. Conclusion: Nutraceuticals are being continuously used in the treatment of various diseases. The future of nutraceuticals is bright and can transform health care. More studies need to be taken up on the prescription of nutraceuticals in health care.

An AI Approach to Identifying Novel Therapeutics for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that has a significant impact on quality of life and work capacity. Treatment of RA aims to control inflammation and alleviate pain; however, achieving remission with minimal toxicity is frequently not possible with the current suite of drugs. This review aims to summarise current treatment practices and highlight the urgent need for alternative pharmacogenomic approaches for novel drug discovery. These approaches can elucidate new relationships between drugs, genes, and diseases to identify additional effective and safe therapeutic options. This review discusses how computational approaches such as connectivity mapping offer the ability to repurpose FDA-approved drugs beyond their original treatment indication. This review also explores the concept of drug sensitisation to predict co-prescribed drugs with synergistic effects that produce enhanced anti-disease efficacy by involving multiple disease pathways. Challenges of this computational approach are discussed, including the availability of suitable high-quality datasets for comprehensive analysis and other data curation issues. The potential benefits include accelerated identification of novel drug combinations and the ability to trial and implement established treatments in a new index disease. This review underlines the huge opportunity to incorporate disease-related data and drug-related data to develop methods and algorithms that have strong potential to determine novel and effective treatment regimens.

Ecofriendly HPLC Method for Simultaneous Determination of the Co-Prescribed Drugs in Chemotherapy Omeprazole, Ondansetron and Deflazacort in Spiked Human Plasma.

Green, selective and accurate high-performance liquid chromatography (HPLC) chromatographic method is presented for simultaneous separation and quantitation of the co-prescribed drugs in chemotherapy omeprazole, ondansetron and deflazacort in spiked human plasma. An isocratic HPLC separation was performed on X Bridge C18 (4.6 × 250mm) column with 5μm particle size using mobile phase consisting of methanol: ammonium acetate buffer pH4 adjusted by acetic acid (60: 40, v/v). The injection volume was 20μL with UV detection wavelength at 237nm at room temperature. Flow rate of the mobile phase was adjusted to be 2.0ml/min. Dexamethasone was used as internal standard to correct the variation during sample pretreatment. FDA guidelines were followed to validate the developed method. Successful application of the developed method was revealed by simultaneous determination of omeprazole, ondansetron and deflazacort in spiked human plasma in ranges of 1-20, 0.1-8 and 0.2-8μgmL-1 for omeprazole, ondansetron and deflazacort, respectively. Four greenness assessment tools were used to evaluate the greenness of the developed method and the results were accepted. This method permitted the accurate simultaneous determination of the studied drugs, thus it can be used during therapeutic drug monitoring in daily clinical practice.

Prescription pattern analysis of Type 2 Diabetes Mellitus: a cross-sectional study in Isfahan, Iran

BackgroundPatients with Type 2 Diabetes Mellitus (T2DM) are at a higher risk of polypharmacy and more susceptible to irrational prescriptions; therefore, pharmacological therapy patterns are important to be monitored. The primary objective of this study was to highlight current prescription patterns in T2DM patients and compare them with existing Standards of Medical Care in Diabetes. The second objective was to analyze whether age and gender affect prescription patterns.MethodThis cross-sectional study was conducted using the Iran Health Insurance Organization (IHIO) prescription database. It was mined by an Association Rule Mining (ARM) technique, FP-Growth, in order to find co-prescribed drugs with anti-diabetic medications. The algorithm was implemented at different levels of the Anatomical Therapeutic Chemical (ATC) classification system, which assigns different codes to drugs based on their anatomy, pharmacological, therapeutic, and chemical properties to provide an in-depth analysis of co-prescription patterns.ResultsAltogether, the prescriptions of 914,652 patients were analyzed, of whom 91,505 were found to have diabetes. According to our results, prescribing Lipid Modifying Agents (C10) (56.3%), Agents Acting on The Renin-Angiotensin System (C09) (48.9%), Antithrombotic Agents (B01) (35.7%), and Beta Blocking Agents (C07) (30.1%) were meaningfully associated with the prescription of Drugs Used in Diabetes. Our study also revealed that female diabetic patients have a higher lift for taking Thyroid Preparations, and the older the patients were, the more they were prone to take neuropathy-related medications. Additionally, the results suggest that there are gender differences in the association between aspirin and diabetes drugs, with the differences becoming less pronounced in old age.ConclusionsAlmost all of the association rules found in this research were clinically meaningful, proving the potential of ARM for co-prescription pattern discovery. Moreover, implementing level-based ARM was effective in detecting difficult-to-spot rules. Additionally, the majority of drugs prescribed by physicians were consistent with the Standards of Medical Care in Diabetes.

Potential drug-drug interactions with phentermine among long-term phentermine consumers: A retrospective analysis.

Phentermine is an internationally recognised amphetamine derivative with significant appetite-suppressing properties. The drug is indicated for the short-term management of obesity, as the long-term (LT) use of phentermine may potentially be associated with severe cardiovascular side-effects, abuse and dependence. The LT use hereinafter describes periods exceeding 12consecutive weeks. This use may also be associated with potential drug-drug interactions (PDDIs), which may result in adverse drug reactions (ADRs). The literature reports that phentermine is often prescribed LT and for several other off-label indications, increasing the risk for individuals to experience adverse drug events (ADEs) and drug-drug interactions (DDIs). There are, to our knowledge, no South African (SA) studies investigating the prevalence of co-prescribing LT phentermine with drugs that may potentially cause DDIs. To determine the prevalence of mild, moderate and severe DDIs with phentermine use when the duration of therapy in private healthcare exceeded 12consecutive weeks. A cross-sectional drug utilisation review (DUR) was done by using data obtained from a SA pharmacy benefit management (PBM) company's database. Retrospective data of medicine claims for phentermine, from 1 January 2015 to 31 December 2019, were extracted for analysis. The number of days phentermine was supplied was used to identify the study population, in other words, those patients who received the drug LT. A drug interaction checker (Drugs.com) was used to identify potential mild, moderate and severe DDIs when using phentermine and co-prescribed drugs concurrently. A total of 889 patients received phentermine LT. The top 20 drugs identified as being frequently co-prescribed in this study population demonstrated no mild PDDI, 15 (75%) moderate PDDIs and 5 (25%) severe PDDIs. The most common co-prescribed drug in the moderate group was dextromethorphan (n=282, 31.72%) and the least co-prescribed was formoterol (n=52, 5.85%). Among the drug group 'severe PDDIs', tramadol (n=416, 46.79%) was most frequently prescribed, whereas phenylpropanolamine (n=69, 7.76%) was the least prescribed to patients in this group. There are patients who receive LT phentermine therapy despite the potential severe consequences that may result. These patients may receive concomitant therapy with phentermine and other pharmaceutical constituents, which may potentially cause DDIs, more specifically, moderate and severe DDIs. As such, these patients are not only confronted with the consequences of DDIs but are also at risk to experience ADRs as the residual effect of PDDIs.

Green liquid chromatographic method for simultaneous determination of metformin, linagliptin and rivaroxaban: Tablet manufacturing and application to in-vitro dissolution studies

Single-pill fixed combination therapy enhances patient adherence and facilitates the effective management of asymptomatic conditions such as cardiovascular disease and diabetes etc. Considering the potential need for a fixed triple-dose combination of metformin HCl, linagliptin and rivaroxaban, here we report, fixed-dose film-coated tablet manufacturing of three co-prescribed drugs (metformin HCl, linagliptin, rivaroxaban) and development of assay method for its analysis followed by in-vitro drug release profile. The analysis was performed under isocratic conditions using phosphate buffer (pH 6.8): ACN (70:30) at 1.00 mL min−1 flow rate. The detector wavelength was adjusted at 248 nm. ICH guidelines were followed for method validation. Linearity was found to be 40–1500, 0.2–7.50 and 0.80–30 µg mL−1 with quantification limits 24.05, 0.264 and 0.565 μg mL−1 for metformin HCl, linagliptin and rivaroxaban respectively. The good reproducibility of the developed method confirmed its suitability for its intended use in routine analyses as per pharmaceutical quality control practices. Greenness evaluation of the proposed method using AES score, AMVI, AGREE, and NEMI tools suggested that the method is environment friendly.

Issue Highlights.

Figures from the editors selected issue highlights will be displayed each month in the journal image carousel on the BJCP homepage http://bpspubs.onlinelibrary.wiley.com/hub/journal/10.1111/(ISSN)1365-2125/ One of the first conferences I attended during my time in Leiden was a Modeling and Simulation meeting a few miles outside of Leiden, in Noordwijkerhout, organized by Professor Meindert Danhof. The meeting was a dazzling display of differential equations and brilliant PK/PD models, with one model even more sophisticated and better than the other. It was a time when most lectures were still presented using actual slides, with a few early adapters of power point, if I remember correctly. The best and most memorable lecture of the entire symposium though was not about modeling and simulation. And it was not presented using slides or power point. It was the final plenary lecture of the meeting, and it was presented by an elderly Swedish Professor who had an overhead projector brought to the podium. He placed down an empty overhead projector sheet on which he made small notes with a marker while he presented. He started by complimenting everybody of the M&S community with their brilliant work, but subsequently elegantly explained that our work would have a much, much bigger impact on clinical outcome if we would focus on treatment adherence, and the improvement thereof. And despite the slightly disgruntled feeling it left with the M&S community, everyone wholeheartedly agreed that he was 100% correct. It is therefore great to see that this month's issue of BJCP is about adherence, and more precisely ‘Advancing the management of adherence in the clinical setting’. Adherence is a science in itself, and one that is finally coming of age. Please read the editorial from our guest editors Dan Wright, Klarissa Sinnappah, and Dyfrig Hughes, which provides a nice introduction to a wonderful new Themed Issue. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15722 We are in the business of trying to improve the world. Through research, education, and patient care we try to improve the lives of people. And while our income may be relatively modest, it is all worth it if we see a patient improve as a result of our efforts, at least for me it is. But sometimes even us ‘altruistic’ clinical pharmacologists come across a project that is so noble that it immediately restores any loss of belief in humanity. In a wonderful review David Branford and colleagues from Truro, UK, describe patterns of antiseizure medication prescription in people with intellectual disability and epilepsy. A commendable effort to improve the quality of life of those who benefit from a bit of extra help. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15748 Continuing our efforts to improve the world and ultimately leaving it a better place than we found it, it is worth reading the paper by Valentina Giunchi et al. who implemented a method to timely and cheaply estimate the environmental risk determined by pharmaceutical residues in Italian surface water combining eco-toxicological and consumption data. It is papers such as these that hopefully raise awareness and provide tools to us to decrease the ecological burden from our efforts to improve and sometimes save lives. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15761 But let's not forget that basically all our efforts are geared towards improving the lives of others, whether they are focused on patient care, education, or therapeutics development. Collectively, the rest of the papers in this issue cover all these areas, and this issue of BJCP is therefore once again a good example of the breadth of clinical pharmacology. I will mention just one of these papers. Ying Zhang and colleagues from GSK describe a therapeutics development paper that paves the way for patient care. Using a metabolic probe cocktail, they were able to show in healthy volunteers that their new HIV-1 Maturation Inhibitor, GSK3640254 is unlikely to influence the PK of most other co-prescribed drugs in HIV patients. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15699 I wish you much reading pleasure, and also a wonderful World Conference of Basic and Clinical Pharmacology in Glasgow (should you be able to attend). Have a great summer!

#3386 PROTON-PUMP INHIBITORS AND SERUM CONCENTRATIONS OF UREMIC TOXINS IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Use of proton-pump inhibitors (PPIs) is common in patients with chronic kidney disease (CKD). PPIs and many uremic toxins (UTs) are eliminated by a kidney tubular organic anion transporter system. In a cross-sectional study, we sought to evaluate the association between PPI prescription and serum concentrations of various UTs. Method We studied a randomly selected subgroup of participants in the CKD-REIN prospective cohort (adult patients with a confirmed diagnosis of CKD and estimated glomerular filtration rate (eGFR) <60ml/min/1.73m²) with available frozen samples collected at baseline. PPI prescription was recorded at baseline. Serum concentrations of 10 UTs were measured using a validated liquid chromatography tandem mass spectrometry technique. Multiple linear regression was performed, with the log UT concentration as the dependent variable. Results Of the 680 included patients [median age: 68 years; median eGFR: 32 ml/min/1.73 m2], 31% had PPI prescriptions at baseline. Patients using PPIs had higher levels of certain UTs in comparison to other patients, including total and free indoxyl sulfate (IS), total and free p-cresylsulfate, total and free p-cresylglucuronide (PCG), phenylacetylglutamine (PAG), free kynurenine, and free hippuric acid. After adjustment for baseline comorbidities, number of co-prescribed drugs and laboratory data including eGFR, associations between PPI prescription and elevated serum concentrations of free and total IS, free and total PCG, and PAG remained significant. Conclusion Our results indicate that PPI prescription is independently associated with serum UT retention. These findings indicate a potential mechanism for side effect of PPIs in CKD patients that will need to be confirmed by longitudinal studies.

Proton-Pump Inhibitors and Serum Concentrations of Uremic Toxins in Patients with Chronic Kidney Disease.

Use of proton-pump inhibitors (PPIs) is common in patients with chronic kidney disease (CKD). PPIs and many uremic toxins (UTs) are eliminated by the kidney's tubular organic anion transporter system. In a cross-sectional study, we sought to evaluate the association between PPI prescription and serum concentrations of various UTs. We studied a randomly selected sub-group of participants in the CKD-REIN cohort (adult patients with a confirmed diagnosis of CKD and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) with available frozen samples collected at baseline. PPI prescription was recorded at baseline. Serum concentrations of 10 UTs were measured using a validated liquid chromatography tandem mass spectrometry technique. Multiple linear regression was performed, with the log UT concentration as the dependent variable. Of the 680 included patients (median age: 68 years; median eGFR: 32 mL/min/1.73 m2), 31% had PPI prescriptions at baseline. Patients using PPIs had higher levels of certain UTs in comparison to other patients, including total and free indoxyl sulfate (IS), total and free p-cresylsulfate, total and free p-cresylglucuronide (PCG), phenylacetylglutamine (PAG), free kynurenine, and free hippuric acid. After adjustment for baseline co-morbidities, number of co-prescribed drugs, and laboratory data, including eGFR, associations between PPI prescription and elevated serum concentrations of free and total IS, free and total PCG, and PAG remained significant. Our results indicate that PPI prescription is independently associated with serum UT retention. These findings are interesting to better understand the factors that may modulate serum UT concentration in CKD patients, however, they will need to be confirmed by longitudinal studies.

Clinically significant drug interactions between antiretroviral and co-prescribed drugs in HIV infected patients: retrospective cohort study.

IntroductionThere are limited data on human immunodeficiency viruses (HIV) infected people in the UAE and the Gulf region. This study aimed at assessing the prevalence and risk factors for potential clinically significant drug interactions (CSDIs) in a cohort of 181 HIV infected people in Dubai.MethodsA retrospective study was conducted at the outpatient infectious diseases clinic of Rashid hospital. Consecutive HIV seropositive people on anti-retroviral therapy (ART) were included. All potential CSDIs were analyzed and classified using Liverpool HIV drug interactions database.ResultsNucleoside reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs) were the most frequently used antiretroviral agents (ARVs), while the most common (non-ARV) were cardiovascular medication followed by antilipidemic statins. A total of 140 potential CSDIs were found in nearly half (n=86, 47.5%) of the 181 included HIV persons. Of the 140 potential CSDIs, 27 (19%) were of weak clinical relevance, 108 (77%) were of potential clinical relevance, and 5 (4%) were of contraindicated clinical relevance interactions. Moreover, 52 (37.14%) of CSDIs were between two ARVs and 88 (62.85%) were between ARV and non-ARV drugs. In the univariate analysis, age, dyslipidemia, number of medications, analgesics use, statin use, supplement intake, time since diagnosis of HIV, number of ART, and use of a protease inhibitor (PI) were significant. In the logistic regression, factors independently associated with CSDIs were the number of medications (odds ratio [OR] 1.165, 95% CI 1.021–1.329, P = 0.023) and the time since diagnosis of HIV (OR 1.156, 95% CI 1.008–1.327, P = 0.038).ConclusionThe frequency of CSDIs between ART and co-medications is high in HIV seropositive people. Awareness of the risk factors may assist clinicians to recognize and manage CSDIs.

Do drugs interact together in cardiovascular prevention? A meta-analysis of powerful or factorial randomized controlled trials

To explore whether preventive cardiovascular drugs (antihypertensive, antiplatelet, lipid lowering and hypoglycemic agents) interact together in cardiovascular prevention. We searched PubMed®, Web of science™, Embase and Cochrane library for powerful randomized placebo-controlled trials (>1000 patients). We explored whether drug effect on major vascular events changed according to cross-exposure to other drug classes or to cardiovascular risk factors (hypertension or type 2 diabetes), through a meta-analysis of relative odds ratio computed by trial subgroups. A significant interaction was suggested from confidence intervals of the ratio of odds ratios, when they excluded neutral value of 1. In total, 14 trials with 178,398 patients were included. No significant interaction was observed between co-prescribed drugs or between these medications and type 2 diabetes/hypertension status. Our meta-analysis is the first one to evaluate drug-drug and drug-hypertension/type 2 diabetes status interactions in terms of cardiovascular risks: we did not observe any significant interaction. This indirectly reinforces the rationale of using several contrasted mechanisms to address cardiovascular prevention; and allows the combination effect prediction by a simple multiplication of their odds ratios. The limited availability of data reported or obtained from authors is a strong argument in favor of data sharing.

Warfarin Pharmacogenomics for Precision Medicine in Real-Life Clinical Practice in Southern Africa: Harnessing 73 Variants in 29 Pharmacogenes.

Pharmacogenomics is universally relevant for worldwide modern therapeutics and yet needs further development in resource-limited countries. While there is an abundance of genetic association studies in controlled medical settings, there is a paucity of studies with a naturalistic design in real-life clinical practice in patients with comorbidities and under multiple drug treatment regimens. African patients are often burdened with communicable and noncommunicable comorbidities, yet the application of pharmacogenomics in African clinical settings remains limited. Using warfarin as a model, this study aims at minimizing gaps in precision/personalized medicine research in African clinical practice. We present, therefore, pharmacogenomic profiles of a cohort of 503 black Africans (n = 252) and Mixed Ancestry (n = 251) patients from Southern Africa, on warfarin and co-prescribed drugs in a naturalized noncontrolled environment. Seventy-three (n = 73) single nucleotide polymorphisms (SNPs) in 29 pharmacogenes were characterized using a combination of allelic discrimination, Sanger sequencing, restriction fragment length polymorphism, and Sequenom Mass Array. The common comorbidities were hypertension (43–46%), heart failure (39–45%), diabetes mellitus (18%), arrhythmia (25%), and HIV infection (15%). Accordingly, the most common co-prescribed drugs were antihypertensives, antiarrhythmic drugs, antidiabetics, and antiretroviral therapy. We observed marked variation in major pharmacogenes both at interethnic levels and within African subpopulations. The Mixed Ancestry group presented a profile of genetic variants reflecting their European, Asian, and African admixture. Precision medicine requires that African populations begin to capture their own pharmacogenetic SNPs as they cannot always infer with absolute certainty from Asian and European populations. In the current historical moment of the COVID-19 pandemic, we also underscore that the spectrum of drugs interacting with warfarin will likely increase, given the systemic and cardiovascular effects of COVID-19, and the anticipated influx of COVID-19 medicines in the near future. This observational clinical pharmacogenomics study of warfarin, together with past precision medicine research, collectively, lends strong support for incorporation of pharmacogenetic profiling in clinical settings in African patients for effective and safe administration of therapeutics.

A machine learning framework for predicting drug\u2013drug interactions

Understanding drug–drug interactions is an essential step to reduce the risk of adverse drug events before clinical drug co-prescription. Existing methods, commonly integrating heterogeneous data to increase model performance, often suffer from a high model complexity, As such, how to elucidate the molecular mechanisms underlying drug–drug interactions while preserving rational biological interpretability is a challenging task in computational modeling for drug discovery. In this study, we attempt to investigate drug–drug interactions via the associations between genes that two drugs target. For this purpose, we propose a simple f drug target profile representation to depict drugs and drug pairs, from which an l2-regularized logistic regression model is built to predict drug–drug interactions. Furthermore, we define several statistical metrics in the context of human protein–protein interaction networks and signaling pathways to measure the interaction intensity, interaction efficacy and action range between two drugs. Large-scale empirical studies including both cross validation and independent test show that the proposed drug target profiles-based machine learning framework outperforms existing data integration-based methods. The proposed statistical metrics show that two drugs easily interact in the cases that they target common genes; or their target genes connect via short paths in protein–protein interaction networks; or their target genes are located at signaling pathways that have cross-talks. The unravelled mechanisms could provide biological insights into potential adverse drug reactions of co-prescribed drugs.

Current Surgical Antibiotic Prophylaxis Practices: A Survey of Orthopaedic Surgeons in India.

Surgical antibiotic prophylaxis (SAP) has become the standard of care in orthopaedic surgery. Inappropriate usage of antibiotics (dosage, strength, and/or administration time and duration) can inadvertently result in superadded infections and antimicrobial resistance. The purpose of this study was to document and analyse the prescription patterns for SAP, and to investigate the factors associated with divergence from standard guidelines. We conducted an online cross-sectional questionnaire-based study to collect information about the SAP practices of the members of the Indian Orthopaedic Association (IOA) using Google forms. A link to the questionnaire was sent by e-mails. The overall response rate was 5.73%. While 97.3% respondents practised SAP routinely, the practice was not aligned with standard guidelines' recommendations. There was heterogeneity in the use of SAP in terms of choice of antibiotic(s), number of co-prescribed drugs, single- versus multiple-dose regimens, and the duration of therapy. The prescription practice patterns showed that orthopaedic surgeons almost always used broad-spectrum antibiotics for long durations, regardless of the type of surgery. While Orthopaedic surgeons in India are practicing SAP, the pattern of antibiotic usage is heterogeneous. Variations were noted in the choice of antibiotics for different types of surgeries, time of administration, duration of usage in the postoperative period as well as co-prescriptions. This study highlights the urgent need for a comprehensive, rational, and robust national SAP policy for orthopaedic surgeries.

Ecofriendly chromatographic methods for determination of co-prescribed drugs, olanzapine and metformin, in rat plasma.

Background: Olanzapine (OLZ) is one of most recommended drugs for the treatment of schizophrenia while metformin (MET) is the most commonly used hypoglycemic agent. Aim: Development and validation of two green, sensitive and accurate chromatographic methods for the simultaneous determination of OLZ along with the co-prescribed, MET. Materials & methods: TLC-densitometric method with a developing system consisting of methylene chloride:methanol:ethyl acetate:triethylamine (4:4:5:0.1, by volume) and a reversed-phase (RP)-HPLC method where the chromatographic separation was performed using ethanol:water mixture (50: 50, v/v) as a mobile phase. Results: TLC-densitometric method had linearity over concentration ranges of 160-4000ng/band for OLZ and 150-4500ng/band for MET, while RP-HPLC method was linear and validated over concentration range of 300-20000ng/ml for OLZ and MET. Conclusion: Pharmacokinetic study was successfully performed and suggested the possibility of co-administration of MET with OLZ and their further formulation in one pharmaceutical preparation to enhance patient's compliance.

A super-combo-drug test to detect adverse drug events and drug interactions from electronic health records in the era of polypharmacy.

Pharmacoinformatics research has experienced a great deal of successes in detecting drug-induced adverse events (AEs) using large-scale health record databases. In the era of polypharmacy, pharmacoinformatics faces many new challenges, and two significant challenges are to detect high-order drug interactions and to handle strongly correlated drugs. In this article, we propose a super-combo-drug test (SupCD-T) to address the aforementioned two challenges. SupCD-T detects drug interactions by identifying optimal drug combinations with increased AE risks. In addition, SupCD-T increases the statistical powers to detect single-drug effects by combining strongly correlated drugs. Although SupCD-T does not distinguish single-drug effects from their combination effects, it is noticeably more powerful in selecting an individual drug effect in the multiple regression analysis, where confounding justification between two correlated drugs reduces the power in testing the individual drug effects on AEs. Our simulation studies demonstrate that SupCD-T has generally better power comparing with the multiple regression analysis. In addition, SupCD-T is able to select meaningful drug combinations (eg, highly coprescribed drugs). Using electronic health record database, we illustrate the utility of SupCD-T and discover a number of drug combinations that have increased risk in myopathy. Some novel drug combinations have not yet been investigated and reported in the pharmacology research.

Is There an Association Between Antiepileptic Drug Use and Dementia Risk? A Case-Control Study.

Previous research has found a positive association between the use of antiepileptic drugs (AEDs) and dementia. However, there have been some concerns about the generalizability of its findings. The goal of this case-control study was to analyze the association between AED use and dementia risk in Germany. This study included patients who had received a first dementia diagnosis from one of 1,203 general practitioners or 202 neuropsychiatrists between 2013 and 2017 (index date). Controls without dementia were matched (1:1) to dementia cases by age, gender, physician, diagnosis of mild cognitive impairment, and observation time prior to the index date. Two regression models were used to analyze the association between AED use and dementia risk after adjusting for comorbidities and co-prescribed drugs. AEDs were included as a dichotomous variable in Model 1 (ever versus never use) and as a continuous variable in Model 2 (duration of treatment in years). A total of 50,575 cases with dementia and 50,575 controls without dementia were included in this study. Model 1 (odds-ratio [OR] = 0.99) and Model 2 (OR = 1.00) showed no significant association between AED use and dementia risk. However, prescriptions for levetiracetam generic brands (Model 1: OR = 1.70; Model 2: OR = 1.36) were associated with an increased dementia risk. Overall, AED use was not significantly associated with dementia risk in patients followed by general practitioners and neuropsychiatrists in Germany between 2013 and 2017. Nonetheless, the potential deleterious effects of levetiracetam generic brands on cognition deserve further investigation.

Characteristics of patients with thromboembolic disorders on warfarin therapy in resource limited settings

BackgroundWarfarin is a drug with narrow therapeutic index used in the management of thromboembolic disorders. Several factors affect its plasma concentrations with a resultant risk of toxicity. We examined the database of patients on warfarin therapy in order to establish the factors that affect the stability of INR and correlated them to clinical outcomes in resource limited settings.MethodsWe analysed retrospective data of patients admitted to adult medical wards at Moi Teaching and Referral Hospital (MTRH) in 2015. Inclusion criteria were patients with thromboembolic and related disorders and on warfarin treatment. Derived data included demographics, indications for warfarin use, co-prescribed drugs, co-morbidities, INR measurements, duration of hospital stay and clinical outcomes. Descriptive statistics were used to summarize the data. Pearson’s correlation coefficient was used to assess relationships between duration of hospitalization and number of INR tests. Regression splines were used to capture INR trends during the follow up period. Data was analysed using R v. 3.3.1.ResultsA total of 310 patients had thromboembolic disorders, out of which 63 met the study criteria.The median age was 48 years, while the mean number of INR measurements was once every four days. Majority of patients did not achieve stable INR values, with only two having consecutive INR values within therapeutic goal. Patients who died had high INR levels. The median duration of hospital stay was 9 days (IQR: 7.0, 16.5). There was a significant correlation between length of stay in hospital and the number of times that INR were measured (Corr = 0.667, p < 0.001). The two most common indications for warfarin were DVT (64.4%) and atrial fibrillation (24.7%). All the patients had one or more comorbid conditions except for 11 with DVT alone, with cardiovascular diseases and infections being the most frequent, and on concomitant medications, majority of which are known to interact with warfarin.ConclusionsIt was difficult to achieve stable INR under the prevailing conditions despite the frequent tests.The potential factors that may have contributed to the fluctuations include drug-drug interactions, frequency of INR tests, comorbidities and the short duration of hospital stay.

Non-Steroidal Anti-Inflammatory Drugs Prescription in Elderly Ambulatory Patients

Non-steroidal antiinflammatory drugs (NSAID) are widely used medications in elderly ambulatory patients despite their numerous side effects. The NSAID prescription by 6 general practitioners (GPs) working in a single center to ambulatory patients aged 65 years or older was retrospectively evaluated. Individual interviews of the 6 GPs were performed by means of qualitative questionnaires to determine NSAID prescription habits, knowledge of NSAID by doctors, knowledge of Good Clinical Practice (GCP) recommendations. We then conducted a retrospective observational study in 154 patients aged 65 years or older who received at least one NSAID given orally between October 1st and December 31st of 2014, by means of a questionnaire including 34 validated evaluation criteria according to the current guidelines. The 6 GPs did not frequently prescribe NSAID in their patients aged 65 years or older, due to the high number of co-prescribed drugs, renal or liver insufficiency, and the high risk of side effects in these patients. Their knowledge regarding the side effects, contra-indications and warnings of the various available NSAIDs are heterogeneous and none of the interviewed GPs were aware of available GCP recommendations regarding NSAIDs prescription and side effects prevention in older patients. 10.5% of the 154 patients had a prescription of at least one NSAID. However, this prescription was in agreement with the market authorization recommendation in only 72% of cases. Numerous gaps were identified between daily practice of these GPs and the available GCP recommendations, except for the recommendations regarding gastrointestinal side effects and contra-indications of the NSAID, which were highly respected. GCP recommendations for NSAIDs prescription are unknown from prescribers and respect of these recommendations should be improved by means of a patient-dedicated follow-up file designed to optimize the management and prevention of NSAID-related side effects in daily practice.

Characterizing Potentially Inappropriate Prescribing of Proton Pump Inhibitors in Older People in Primary Care in Ireland from 1997 to 2012.

To characterize prescribing of proton pump inhibitors (PPIs) and medicines that increase gastrointestinal bleeding risk (ulcerogenic) in older people from 1997 to 2012 and assess factors associated with maximal-dose prescribing in long-term PPI users. Repeated cross-sectional study of pharmacy claims data. Eastern Health Board region of Ireland. Individuals aged 65 and older from a means-tested health plan in 1997, 2002, 2007, and 2012 (range 78,489-133,884 individuals). PPI prescribing prevalence was determined per study year, categorized according to duration (≤8 or >8 weeks), dosage (maximal or maintenance), and co-prescribed drugs. Logistic regression in long-term PPI users was used to determine whether age, sex, polypharmacy, and ulcerogenic medicine use were associated with being prescribed a maximal dose rather than a maintenance dose. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) are presented. Half of this older population received a PPI in 2007 and 2012. Long-term use (>8 weeks) of maximal doses rose from 0.8% of individuals in 1997 to 23.6% in 2012. Although some ulcerogenic medicines and polypharmacy were significantly associated with maximal PPI doses, any nonsteroidal anti-inflammatory drug use was significantly associated with lower odds of maximal PPI dose (adjusted OR = 0.87, 95% CI = 0.85-0.89), as were aspirin use and older age. Adjusting for medication and demographic factors, odds of being prescribed a maximal PPI dose were significantly higher in 2012 than in 1997 (adjusted OR = 6.30, 95% CI = 5.76-6.88). Long-term maximal-dose PPI prescribing is highly prevalent in older adults and is not consistently associated with gastrointestinal bleeding risk factors. Interventions involving prescribers and patients may promote appropriate PPI use, reducing costs and adverse effects of PPI overprescribing.