Fate of pharmaceutical residue in two Romanian rivers receiving treated water: Occurrence, distribution and risk assessment.

This study presents the first set of data on the removal of proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (HRAs) and their transformation products in two Romanian wastewater treatment plants (WWTPs), as well as the impact of these organic pollutants on freshwater receiving effluents. The research investigated eight target pharmaceuticals and three metabolites using a newly developed and validated Liquid Chromatography - Mass Spectrometry (LC-MS/MS) method. The combined determination had a range of quantification limits varying from 0.13 ng/L to 0.18 ng/L for surface water and from 0.28 ng/L to 0.43 ng/L for wastewater. All analytes except cimetidine and 5-hydroxy-omeprazole were identified in water samples. The study found similar overall removal efficiencies for both WWTPs (43.2 % for Galati and 51.7 % for Ramnicu-Valcea). The research also showed that ranitidine and omeprazole could pose a low to high ecological risk to aquatic organisms. The findings suggest that the treatment stages used in the two Romanian WWTPs are insufficient to remove the target analytes completely, leading to environmental risks associated with the occurrence of pharmaceutical compounds in effluents and freshwater.

Trend analysis of proton pump inhibitor consumption and expenditure: The real-world evidence.

INTRODUCTION: Proton pump inhibitors (PPIs) constitute a widely utilized pharmaceutical class, frequently associated with notable instances of therapeutic inappropriateness. Such patterns of misuse not only contribute to elevated healthcare expenditure, but may also exacerbate clinical conditions in certain patients. METHODS: A comprehensive analysis was conducted between 2019 and 2023 to assess all prescriptions dispensed using the Anatomical, Therapeutic and Chemical (ATC) classification system, which allowed trends among primary PPIs to be visualized. This was achieved by calculating the defined daily dose (DDD) and then defining the total expenditure incurred on these drugs. RESULTS: With regard to the prescription of PPIs, an upward trend in consumption was observed with a decreasing expenditure, due to the phenomena of drug generics and increased competition between pharmaceutical companies, ranging from €9,512,481.22 in the first six months of 2019 to €8,509,820.80 in the first six months of 2023. From 2019 to 2023, consumption increased by approximately 3 million DDDs for a total ranging from 18,483,167.59 DDDs to 21,480,871.00 DDDs. Pantoprazole and esomeprazole, the most expensive drugs compared to omeprazole, rabeprazole and lansoprazole, accounted for 61.4% of therapies in the first six months of 2023, up from 2019, where these two drugs were prescribed 54.9%. CONCLUSION: Within this analysis, we provide an illustrative representation of the prescribing trends for PPIs within a European context. Omeprazole, rabeprazole and lansoprazole appear to be the cheapest drugs compared to pantoprazole and esomeprazole. However, the results show that the most widely used PPIs, despite their therapeutic equivalence, are precisely the high-cost ones, thus generating higher expenditure for central governments.

The Impact of Prescribing Monitoring Policy on Drug Use and Expenditures in China: A Multi-center Interrupted Time Series Study.

BACKGROUND: A prescribing monitoring policy (PMP) was implemented in November 2015 in Anhui province, China, the first province to pilot this policy to manage the use and costs of select drugs based on their large prescription volumes and/ or costs in hospitals. This study evaluated the impact of PMP on the use and expenditures of different drugs in three tertiary hospitals in Anhui. METHODS: We obtained monthly drug use and expenditures data from three tertiary hospitals in Anhui (November 2014 through September 2017). An interrupted time series (ITS) design was used to estimate changes in defined daily doses (DDDs per month) and drug expenditures (dollars per month) of policy-targeted and non-targeted drugs after PMP implementation. Drugs were grouped based on whether they were recommended (recommended drugs) by any clinical guidelines or not (non-recommended drugs), or if they were potentially over-used (proton pump inhibitors, PPIs). RESULTS: After PMP, DDDs and costs of the targeted PPIs (omeprazole) declined while use of non-targeted PPIs increased correspondingly with overall sustained declines in total PPIs. The policy impact on recommended drugs varied based on whether the targeted drugs have appropriate alternatives. The DDDs and costs of recommended drugs that have readily accessible appropriate alternatives (atorvastatin) declined, which offset increases in its alternative non-target drugs (rosuvastatin), while there was no significant change in those recommended drugs that did not have appropriate alternative drugs (clopidogrel and ticagrelor). Finally, the DDDs and costs of non-recommended drugs decreased significantly. CONCLUSION: PMP policy impact was not the same across different drug groups. PMP did help contain the use and costs of potentially over-used drugs and non-recommended drugs. PMP did not seem to reduce the use of first-line therapeutic drugs recommended by clinical treatment guidelines, especially those lacking alternatives; such drugs are unlikely appropriate candidates for PMP.

Assessment of gastrointestinal health in racing Alaskan sled dogs using capsule endoscopy and inflammatory cytokines.

OBJECTIVES: Exercise-induced gastrointestinal syndrome occurs in dogs and people and might compromise athlete performance by increasing intestinal permeability and causing gastrointestinal erosions. Racing sled dogs often receive acid suppressant prophylaxis which decreases the incidence of gastric erosions induced by exercise. The objectives were to quantify intestinal injury by measuring serum pro-inflammatory cytokine concentrations before and after exercise and to evaluate gastrointestinal mucosa using video capsule endoscopy after exercise. MATERIALS AND METHODS: Prospective study of 12 racing Alaskan sled dogs receiving approximately 1 mg/kg omeprazole once daily from the day before the race until race completion. Blood was drawn before and 8 to 10 hours after an endurance race for the quantification of cytokines. Gastrointestinal tract mucosa was assessed with video capsule endoscopy immediately post-race. RESULTS: Eight of nine dogs (89%; 95% confidence interval 52 to 100%) had gastric erosions; all dogs (100%, 95% confidence interval 63 to 100%) had small intestinal erosions. Most of the dogs (seven of nine) had straw or foreign material present. Cytokine levels were not different from before to after the race. CLINICAL SIGNIFICANCE: Video capsule endoscopy identified gastrointestinal tract mucosal erosions after exercise in all dogs receiving once-daily omeprazole treatment, though other causes for the lesions besides exercise are possible.

Trends in prescribing volumes and costs of proton pump inhibitors in three outpatient specialties: a three-year retrospective study in a tertiary hospital in Thailand.

OBJECTIVES: The study determined a comparative three-year trend in prescribing volumes and costs of proton pump inhibitors in three outpatient specialties of a tertiary hospital. METHODS: Prescription data for three consecutive fiscal years (2016-2018) were extracted from a tertiary hospital electronic database, for the gastrointestinal, cardiovascular and orthopaedic outpatient specialties. The data collected were individual proton pump inhibitors, overall and individual prescribing volumes (capsule/tablet) and costs, stratified by specialty and fiscal year. KEY FINDINGS: Of the three specialties, the largest volume of proton pump inhibitor prescriptions, mostly for omeprazole, comes from the orthopaedic specialty (46%). In terms of prescribing costs, at the top is the cardiovascular specialty (45.75%). Lansoprazole, which is one of the proton pump inhibitors on in the national list of essential medicines, contributed most to the cost. Prescribing proton pump inhibitors that are not included in the national list of essential medicines were responsible for over 90% of the costs in the cardiovascular and gastrointestinal specialties. An escalating trend in prescribing varied proton pump inhibitors, that is, esomeprazole, lansoprazole, pantoprazole, dexlansoprazole and rabeprazole, all of which were not on the list of essential medicines, was evident in the latter. CONCLUSIONS: The highest volume of proton pump inhibitor prescribing-mostly of omeprazole, was issued by the orthopaedic specialty. The cardiovascular specialty was responsible for the largest amount of cost. The increases in the uses and costs of varying proton pump inhibitors which were outside the national list of essential medicines were notable in the gastrointestinal specialty.

Physicochemical Equivalence and Quality Assessment of Various Brands of Gastro-Resistant Omeprazole Capsules in the Kumasi Metropolis.

The proliferation of counterfeit and poor-quality drugs is a major public health problem, especially in developing countries such as Ghana where there are inadequate resources to effectively monitor their prevalence. Most of these drugs, which are counterfeited, are drugs, which are in high demand and will reap huge profits for the unscrupulous people who engage in such activities. The introduction of Omeprazole as one of the first-line therapies in the management of peptic and duodenal ulcers in the treatment guidelines of Ghana has resulted in many generics being introduced onto the market. The pharmaceutical quality of fifteen randomly sampled Omeprazole capsule brands in the Kumasi metropolis was assessed using the innovator brand as a comparator to confirm their suitability for patient use and to provide data for drug regulatory agencies in Ghana concerning poor quality omeprazole brands. All the sampled brands complied with the official specifications for identification with good primary and secondary packaging characteristics. Ninety-four (94%) of the sampled brands passed the uniformity of weight test. All the brands (n = 16) representing 100% passed the disintegration tests. Sixty percent (60%) of the sampled brands passed the drug content test. Ten brands (66.7%) met the specification for in vitro dissolution test. From f2 analysis, the dissolution profiles of only five brands (31%) were similar to that of the reference brand which indicated that they could be used interchangeably in clinical practice. Conclusively, ten out of the fifteen sampled brands were of good quality and only five could be used as a substitute for the innovator. Thus, regulatory agencies will need to strengthen their postmarket surveillance to ensure that generic brands of good quality are allowed onto the market.

Skeletal muscle relaxant drug-drug-drug interactions and unintentional traumatic injury: Screening to detect three-way drug interaction signals.

AIM: The aim of this study was to identify skeletal muscle relaxant (SMR) drug-drug-drug interaction (3DI) signals associated with increased rates of unintentional traumatic injury. METHODS: We conducted automated high-throughput pharmacoepidemiologic screening of 2000-2019 healthcare data for members of United States commercial and Medicare Advantage health plans. We performed a self-controlled case series study for each drug triad consisting of an SMR base-pair (i.e., concomitant use of an SMR with another medication), and a co-dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base-pair. We included patients aged ≥16 years with an injury occurring during base-pair-exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base-pair + candidate interacting precipitant (i.e., triad) versus the SMR-containing base-pair alone. RESULTS: Among 58 478 triads, 29 were significantly positively associated with injury; confounder-adjusted RRs ranged from 1.39 (95% CI = 1.01-1.91) for tizanidine + omeprazole with gabapentin to 2.23 (95% CI = 1.02-4.87) for tizanidine + diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated. CONCLUSION: We identified 29 SMR 3DI signals associated with increased rates of injury. Future aetiologic studies should confirm or refute these SMR 3DI signals.

Verification of a cocktail approach for quantitative drug-drug interaction assessment: a comparative analysis between the results of a single drug and a cocktail drug.

A cocktail approach is a method to comprehensively evaluate the activity of cytochrome P450 enzymes (CYPs) by co-administering multiple CYP substrates. This is the first report that compares the results from a cocktail study to a single substrate separate administration study (single study) with concomitant administration of CYP inducers/inhibitors. The validity of a cocktail study for use as a quantitative drug-drug interactions (DDIs) assessment was evaluated.We administered a cocktail drug (caffeine, losartan, omeprazole, dextromethorphan, midazolam) with rifampicin, cimetidine or fluvoxamine. A comparative analysis was performed between the results of a cocktail study and single studies. The results of single studies were obtained from a literature review and the trials of single substrate separate administration.A strong positive correlation of the AUC ratio of all drugs between single studies and the cocktail study was obtained. The ratio of AUC change of 12 combinations converged to 0.82-1.09, and 2 combinations ranged between 0.74-1.32.The differences in the degree of interaction between the single studies and cocktail study are acceptable to evaluate DDIs for almost all combinations. Our results indicate that a cocktail study is an adequate and quantitative evaluation method for DDIs.

Omeprazole prescriptions for older adults in health care units in Curitiba, Brazil: an analysis based on Beers Criteria / Prescrições de omeprazol para idosos em unidades de saúde de Curitiba: análise segundo os Critérios de Beers

OBJECTIVE: To evaluate omeprazole prescriptions for older adults based on the Beers Criteria, with an analysis of indications and duration of use longer than eight weeks. METHODS: In this retrospective cross-sectional study, data were collected from the electronic medical records of older adults with an omeprazole prescription seen at two health care units in Curitiba, Brazil, between June and August 2019. Data were subjected to descriptive statistical analysis, Student t and χ2 tests. RESULTS: Medical records of 386 patients were analyzed, and 69.95% were female. The mean age was 71 (SD, 8.15) years. Most patients had incomplete primary education (50.52%) and income level ranging from one to two Brazilian minimum monthly wages (39.90%). No indication for omeprazole prescription was found in 23.83% of medical records. Use longer than eight weeks was predominant for all indications in 96.60% of medical records. Duration of use more extended than the Beers Criteria recommendation was independent of sex (p = 0.327), education (p = 0.805), and income level (p = 0.629). A relationship between polypharmacy and long-term drug use was demonstrated (p < 0.001). CONCLUSION: The results of this study suggest the need for periodic review of omeprazole prescriptions considering deprescribing when they appropriate.

OBJETIVO: Avaliar as prescrições de omeprazol para idosos de acordo com os Critérios de Beers, por meio das indicações e do tempo de uso do medicamento por período superior a oito semanas. METODOLOGIA: Estudo transversal, retrospectivo, no qual foram coletados dados dos prontuários eletrônicos de idosos com prescrição de omeprazol atendidos entre junho e agosto de 2019 em duas unidades de saúde em Curitiba. Os dados foram submetidos à análise estatística descritiva e aos testes t de Student e do χ2 . RESULTADOS: Foram analisados prontuários de 386 usuários, sendo 69,95% do sexo feminino. A média de idade foi de 71 anos (DP, 8,15). A maioria dos usuários tem ensino fundamental incompleto (50,52%) e faixa de renda de um a dois salários mínimos (39,90%). Não foi encontrada a indicação para a prescrição de omeprazol em 23,83% dos prontuários. O uso por período superior a oito semanas foi predominante, para todas as indicações, em 96,60% dos prontuários. Demonstrou-se que o tempo de uso superior ao recomendado nos Critérios de Beers independe do sexo (p = 0,327), da escolaridade (p = 0,805) e da faixa de renda (p = 0,629). Evidenciou-se a relação entre polifarmácia e uso do medicamento por períodos prolongados (p < 0,001). CONCLUSÃO: Os resultados deste estudo apontam para a necessidade de revisão periódica das prescrições de omeprazol, considerando-se a desprescrição quando apropriado.

Prospective observational study of the use of omeprazole and maropitant citrate in veterinary specialist care.

The proton pump inhibitor omeprazole is administered to dogs with gastroduodenal ulceration or oesophagitis, whereas the neurokinin-1 receptor antagonist maropitant citrate is licensed as an antiemetic drug. In people, omeprazole is overprescribed in hospitals, increasing the risk of adverse effects and imposing unnecessary costs in healthcare. To investigate the use of omeprazole and maropitant in our veterinary specialist hospital, we conducted a prospective observational study in its Medicine and Surgery wards, recording patient data and obtaining contemporaneous information from clinicians about their reasons for administering either drug. In doing so, we find omeprazole and maropitant are administered to a large proportion of dogs, including to many of those with no presenting signs suggestive of gastrointestinal disease. We find prescribing clinicians consider both drugs safe but often underestimate their financial cost. We find the stated reasons and objective predictors of administration of both drugs vary according to clinical setting but that these modalities yield concordant results. Reviewing the manner of administration and stated indications for use of both drugs, we find omeprazole is often administered outside dosing recommendations, and both drugs are frequently administered for aims that are unlikely to be achieved when considering their known biological effects in dogs. In conclusion, our work reveals probable overprescribing of omeprazole and maropitant citrate in hospitalised dogs, highlighting a need for initiatives to decrease inappropriate prescribing.

A Drug Content, Stability Analysis, and Qualitative Assessment of Pharmacists' Opinions of Two Exemplar Extemporaneous Formulations.

Despite a decline in the number of active pharmaceutical ingredients prepared extemporaneously using proprietary products, there remains a need for such products in the community (for example, liquid medicines for paediatrics which may be otherwise commercially unavailable). A lack of experience and quality assurance systems may have diminished pharmacist's confidence in the extemporaneous preparation process; therefore, pharmacists were asked to prepare two proprietary products, omeprazole and amlodipine. The resulting products were characterised in terms of variability in drug quantity, stability, particle size and antimicrobial properties. Furthermore, a self-administered questionnaire was used to assess 10 pharmacists' opinions on the perceived complexity of the extemporaneous compounding process and their overall confidence in the final extemporaneously compounded products. Drug content studies revealed that 88.5% and 98.0% of the desired drug content was obtained for omeprazole and amlodipine, respectively. Antimicrobial properties were maintained for both drugs, however variability in particle size, particularly for amlodipine, was evident between formulations. While pharmacists who partook in the study had some or high confidence in the final products, they reported difficulty formulating the suspensions. Findings from this study provide insight into pharmacists' views on two extemporaneously prepared products and highlight the variability obtained in preparations prepared by different pharmacists.

Informe diário de evidências COVID-19: busca realizada em 15 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 15, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 6 protocolos.

Assessment of effects of repeated oral doses of fedratinib on inhibition of cytochrome P450 activities in patients with solid tumors using a cocktail approach.

PURPOSE: Fedratinib, an oral selective kinase inhibitor with activity against both wild type and mutationally activated Janus kinase 2, has been approved for the treatment of adult patients with intermediate-2 or high-risk myelofibrosis by the US Food and Drug Administration. In vitro studies indicated that fedratinib was an inhibitor of several cytochrome P450 (CYP) enzymes. The primary objective of this study was to evaluate the effects of repeated doses of fedratinib on the activity of CYP2D6, CYP2C19, and CYP3A4 in patients with solid tumors using a CYP probe cocktail. METHODS: An open-label, one-sequence, two-period, two-treatment crossover study was conducted. Patients were administered a single oral dose cocktail of metoprolol (100 mg), omeprazole (20 mg), and midazolam (2 mg) used as probe substrates for CYP2D6, CYP2C19, and CYP3A4 enzyme activities, respectively, without fedratinib on Day -1 or with fedratinib on Day 15. RESULTS: Coadministration of 500 mg once-daily doses of fedratinib for 15 days increased the mean area under the plasma concentration-time curve from time zero to infinity following a single-dose cocktail containing metoprolol (CYP2D6 substrate), omeprazole (CYP2C19 substrate), and midazolam (CYP3A4 substrate) by 1.77-fold (90% confidence interval [CI] 1.27-2.47) for metoprolol, 2.82-fold (90% CI 2.26-3.53) for omeprazole, and 3.84-fold (90% CI 2.62-5.63) for midazolam, respectively. The mean plasma Day 14/Day 1 ratio of 4ß-hydroxycholesterol, an endogenous biomarker of CYP3A4 activity, was 0.59 (90% CI 0.54-0.66), suggesting a net inhibition of CYP3A4 by fedratinib. CONCLUSION: Fedratinib is a weak inhibitor of CYP2D6, and a moderate inhibitor of CYP2C19 and CYP3A4. These results serve as the basis for dose modifications of these CYP substrate drugs when co-administered with fedratinib.

Efficacy of Omeprazole, Tetracycline, and 4 Times Daily Dosing of Amoxicillin in Helicobacter pylori Eradication in Limited Resource Area in Bhutan: A Prospective Randomized Trial (BHUTAN Study).

Backgrourd: H. pylori-associated gastric cancer is the first cancer-related death in Bhutan. Effective regimen for H. pylori eradication is essential to reduce risk of developing gastric cancer. Clarithromycin is not widely used in this limited resource country. Aim of this study was to evaluate proper regimen and prevalence of antibiotic resistance pattern for H. pylori eradication in Bhutan. METHODS: Five hundred and forty-six patients underwent gastroscopy during GASTROCAMP between October 2014 and April 2015 in Bhutan and 77 patients were enrolled. Four gastric biopsies were obtained for rapid urease test, histopathology, H. pylori culture with Epsilometer test. All H. pylori-positive patients were randomized to receive either 7-day or 14-day of 500 mg amoxicillin four times daily, 500 mg tetracycline four times daily, and 20 mg omeprazole twice daily. RESULTS: Seventy-seven subjects were enrolled (54 females, 23 males, mean age = 45.4 years). Of 77 patients, 52 (67.5%) received 7-day regimen while 25 (32.5%) had 14-day regimen. Prevalence of H. pylori was 38.2%. Antibiotic resistance was 80.0% for metronidazole, 11.1% for levofloxacin and no resistance seen in amoxicillin, tetracycline and clarithromycin. Overall eradication rates of 7-day and 14-day regimens were 51.9% and 80.0%, p = 0.02. Female and age ≥40 years had significantly higher eradication rate when receiving 14-day compared to 7-day regimen (94.1% vs. 45.9%, OR = 18.82; 95% CI 2.26-157.02, p = 0.0007 and 86.7% vs. 50.0%, OR = 6.50; 95% CI 1.25-33.91, p = 0.02, respectively). CONCLUSIONS: Fourteen-day regimen might be an acceptable regimen for H. pylori eradication in limited resource area such as Bhutan. Female and age ≥40 years should receive longer duration of treatment. This 14-day regimen could at least reduce the risk of developing H. pylori-associated diseases especially peptic ulcer with complications and gastric cancer which lead to many deaths in Bhutan.
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The Effect of Manufacturer on the Compounding of Omeprazole Suspensions and Their Stability Assessment.

In New Zealand, there are no liquid formulations of omeprazole commercially available, therefore suspensions must be extemporaneously compounded from solid dosage forms for patients with swallowing difficulties. The funding for solid dosage forms of omeprazole changes frequently, often every one to two years, without consideration of the impact this may have when extemporaneously compounded liquid dosage forms are required. This study examined suspensions compounded from various solid dosage forms of omeprazole with the purpose of identifying suitable quality formulations and evaluating their chemical and physical stability. Six different solid dosage forms of omeprazole that are available in New Zealand, including capsules, tablets, and powder, were used to prepare 2-mg/mL suspensions in 8.4% w/v sodium bicarbonate solution. The suspensions were then assessed visually for quality and by quantifying sedimentation rate over 120 minutes. Two products, stored in amber bottles at either 4°C or 25°C, demonstrated acceptable quality over a 30-day period whilst monitoring physical and chemical stability on day 0, 7, 14, 20, and 30. Four of the formulated suspensions were deemed to be of poor quality due to either a lack of uniformity or rapid sedimentation, attributes that could lead to inaccurate dosing. Acceptable quality suspensions were prepared from Losec and Dr. Reddy's brands of omeprazole 20-mg capsules. For both brands, a change in color was observed after 20 days and 7 days when stored at 4°C and 25°C, respectively. Chemical stability was determined using a stability-indicating high-performance liquid chromatographic method, with >90% of the active remaining for 30 days when kept at 4°C, and 20 days when stored at 25°C. Not all brands are suitable for extemporaneously compounding omeprazole suspensions. Losec and Dr. Reddy's brands of capsules were suitable to prepare quality omeprazole suspensions. Omeprazole suspensions compounded from these products are stable for 20 days if stored at 4°C and protected from light.

Assessment of the potential therapeutic effects of omeprazole in Schistosoma mansoni infected mice.

Schistosomiasis is a neglected chronic parasitic disease with a significant lasting morbidity. Currently, praziquantel (PZQ) is the most efficient drug for schistosomiasis worldwide. However, the possibility of the occurrence of resistance to PZQ is increasing. Therefore, there is a vital need to find new antischistosomal drugs or to increase the efficacy of the existing ones. Omeprazole is a proton pump inhibitor which is reported to have antiparasitic properties. Thus, the aim of this study was to assess the potential therapeutic effects of omeprazole in experimental Schistosoma mansoni infection either alone or in combination with PZQ. For this aim, 80 laboratory bred mice were divided into 3 groups; uninfected control, infected untreated control, and infected and treated at tenth week P.I. The last group was divided into three subgroups that received either PZQ alone, omeprazole alone, or both drugs. The effectiveness of treatment was assessed by adult worm counts, liver egg count, scanning electron microscopy of adult worms, histopathological, and immunohistochemical (GFAP) examination. There was significant reduction of adult worm counts, liver egg counts, size, diameter of hepatic granulomas, hepatic fibrosis, and GFAP expression in the group that received combined treatment as compared to PZQ group. Moreover, the tegumental changes were more evident in the group that received combined treatment. In conclusion, the administration of omeprazole with PZQ improved the efficacy of PZQ in the treatment of Schistosomiasis mansoni.

Mechanistic Assessment of the Effect of Omeprazole on the In Vivo Pharmacokinetics of Itraconazole in Healthy Volunteers.

BACKGROUND AND OBJECTIVE: SUBA-itraconazole and Sporanox are two oral formulations of itraconazole. Drug-drug interactions with omeprazole have been previously reported; however, mechanistic understanding of the pharmacological and physiological interactions of omeprazole with orally administered itraconazole within a population modeling paradigm is lacking. The objective of this analysis was to mechanistically describe and quantify the effect of omeprazole on the pharmacokinetics of itraconazole and its major metabolite, hydroxyitraconazole from the SUBA itraconazole and Sporanox formulations. METHODS: An in vitro-in vivo (IVIV) pharmacokinetic model of itraconazole and hydroxyitraconazole was developed including data from an omeprazole interaction study with SUBA itraconazole. Meta-models of gastric pH for healthy subjects and subjects receiving omeprazole were integrated into the IVIV model to capture omeprazole-mediated gastric pH changes on itraconazole dissolution and absorption. RESULTS: Omeprazole influenced the kinetics of itraconazole through altering the dissolution and absorption due to the pH-dependent solubility of itraconazole, inhibition of efflux transporters, and inhibiting the metabolism of itraconazole and hydroxyitraconazole. The model-predicted population effects of omeprazole on itraconazole from SUBA-itraconazole were to increase the area under the concentration-time curve (AUC0-24) and maximum concentration (Cmax) by 35 and 31%, respectively, and to decrease AUC0-24 and Cmax from Sporanox by 68 and 76%, respectively. CONCLUSION: Unlike SUBA itraconazole, which requires basic pH for itraconazole release, the omeprazole-induced pH-mediated reduction in Sporanox dissolution overrides any increased exposure from the drug-drug interaction at hepatic metabolizing enzymes or efflux transporters. The model presented here is the most complete quantitative description of the pharmacokinetics of itraconazole and hydroxyitraconazole currently available.

Safety assessment of omeprazole use: a review

ABSTRACT BACKGROUND: Risks regarding hospital admission due to adverse drug reactions and drug interactions from use of omeprazole have been reported. The question guiding the present review was "Which adverse events occur in patients using omeprazole in a Food and Drug Administration-approved and/or off-label manner?" It was also proposed to evaluate the safety of use of omeprazole. DESIGN AND SETTING: Qualitative narrative review with critical evaluation, in a public university. METHODS: The PubMed, SCOPUS, LILACS, SciELO, EMBASE and EBSCO databases were searched on July 31, 2018. Studies evaluating adverse events were screened. RESULTS: 72 articles were included, among which 58 reported on adverse drug events (47, adverse drug reactions; 5, drug interactions; and 6, situations of ineffectiveness). 28 adverse drug reactions not described in compendia and drug leaflets were described in these studies: myocardial infarction (6); stroke (2); spontaneous abortion (1); proliferative changes (1); chills (1); heart failure (1); thrombosis (2); and dementia (1), among others. Severe adverse reactions, for instance cardiac problems, Steven-Johnson syndrome and proliferative changes, were identified. The antiplatelet effects of drugs such as clopidogrel, in patients who underwent heart-related surgery, increased the risk of developing cardiac problems, such as cardiovascular death, myocardial infarction and stroke. In newly transplanted patients, decreased absorption of mycophenolate mofetil occurred, thus leading to rejection of transplanted organs. CONCLUSION: Use of omeprazole should be monitored primarily in patients with heart disorders using antiplatelet agents concomitantly, and in newly transplanted patients using mycophenolic acid, in order to avoid serious adverse reactions.

Prescripción-indicación de los inhibidores de la bomba de protones. Costo de la prescripción inadecuada en un primer nivel en Colombia / Prescription-indication of proton pump inhibitors. Cost of inadequate prescription in a first level institution in Colombia

Resumen Introducción: los inhibidores de la bomba de protones (IBP) son medicamentos antiulcerosos que han presentado patrones de uso diferentes a los autorizados, por lo cual se buscó determinar la prescripción-indicación de los IBP en una institución de primer nivel de La Virginia, Risaralda, y el costo de la prescripción inadecuada. Diseño: estudio de prescripción-indicación de medicamentos. Métodos: estudio de prescripción-indicación en pacientes mayores de 18 años con formulación de un IBP atendidos en el Hospital San Pedro y San Pablo de La Virginia, Risaralda, entre el 1 de julio de 2016 al 31 de julio de 2017. Se obtuvo una muestra aleatoria simple proporcional. Se utilizaron las historias clínicas como unidad de análisis. Se incluyeron variables sociodemográficas, comorbilidades, patrones de prescripción-indicación y polifarmacia. Se definió prescripción-indicación adecuada de IBP según la última evidencia científica disponible. Se usó Epi info 7.2 para realizar estadística descriptiva, X2 y una regresión logística binaria (P<0.05). Para el análisis de costos se definió costo de referencia por unidad de IBP y DHD x 1000 habitantes/día. Se contó con aprobación bioética. Resultados: se analizaron 317 pacientes de los cuales 65.6% eran mujeres. El omeprazol fue el IBP más frecuente prescrito (93.7%). Se presentó una prescripción inadecuada en el 46.3% de los pacientes, siendo el servicio de urgencias el que mayor prescripción inadecuada presentó (53.1%). Los principales diagnósticos asociados a la indicación no adecuada de IBP fueron la hipertensión arterial (10%) seguido de la diabetes (6.0%). Siete variables se asociaron con una mayor probabilidad de presentar una prescripción adecuada de un IBP. El costo anual estimado por prescripción inadecuada de IBP fue de COP $446 602 606 DHD x 1000 habitantes/año. Conclusiones: se describe una elevada proporción de prescripción inadecuada de los IBP en la población de un primer nivel de atención, representando un elevado costo para el centro hospitalario. (Acta Med Colomb 2018; 43: 183-191).

Abstract Introduction: Proton Pump Inhibitors (PPIs) are anti-ulcer drugs that have presented patterns of use different from those authorized, which is why it was sought to determine the prescription-indication of PPIs in a first-level institution in La Virginia, Risaralda as well as the cost of inadequate prescription. Design: prescription-indication study of medication. Methods: study of prescription-indication in patients older than 18 years with formulation of a PPI attended at the San Pedro and San Pablo Hospital of La Virginia, Risaralda, between July 1, 2016 and July 31, 2017. A proportional simple random sample was obtained. The clinical histories were used as a unit of analysis. Sociodemographic variables, comorbidities, prescription-indication patterns and polypharmacy were included. Adequate prescription-indication of PPI was defined according to the latest available scientific evidence. Epiinfo 7.2 was used to perform descriptive statistics, X2 and a binary logistic regression (P <0.05). For the cost analysis, reference cost per unit of IBP and DHD x 1000 inhabitants/day was defined. It had bioethical approval. Results: 317 patients were analyzed, of which 65.6% were women. Omeprazole was the most frequent PPI prescribed (93.7%). An inadequate prescription was presented in 46.3% of the patients, being the emergency service the one with the highest inadequate prescription presented (53.1%). The main diagnoses associated with the inappropriate indication of PPI were arterial hypertension (10%) followed by diabetes (6.0%). Seven variables were associated with a higher probability of presenting an adequate prescription of a PPI. The estimated annual cost for inadequate prescription of PPI was COP $446 602 606 DHD x1000 inhabitants/year. Conclusions: a high proportion of inadequate prescription of PPIs is described in the population of a first level of care, representing a high cost for the hospital center. (Acta Med Colomb 2018; 43: 183-191).

A Comprehensive In Vivo and In Vitro Assessment of the Drug Interaction Potential of Red Ginseng.

Purpose: Red ginseng is one of the world's most popular herbal medicines; it exhibits a wide range of pharmacologic activities and is often co-ingested with other herbal and conventional medicines. This open-label, randomized, 3-period study investigated the in vivo herb-drug interaction potential for red ginseng extract with cytochrome P-450 (CYP) enzymes and organic anion-transporting polypeptide (OATP) 1B1. METHODS: Fifteen healthy male volunteers (22-28 years; 57.1-80.8 kg) were administered a single dose of cocktail probe substrates (caffeine 100 mg, losartan 50 mg, omeprazole 20 mg, dextromethorphan 30 mg, midazolam 2 mg, and pitavastatin 2 mg) and single or multiple doses of red ginseng extract for 15 days. FINDINGS: The pharmacokinetic profiles of the probe substrates and metabolites after single- or multiple-dose administration of red ginseng extracts were comparable to the corresponding profiles of the control group. The geometric mean ratio of AUC0-t and 90% CIs for the probe substrate drugs between the control and multiple doses of red ginseng for 15 days were within 0.8 to 1.25 (CYP2C9, CYP3A4, and OATP1B1 probe substrates) or slightly higher (CYP1A2, CYP2C19, and CYP2D6 probe substrates). Additional assessments of the in vitro drug interaction potential of red ginseng extracts and the ginsenoside Rb1 on drug-metabolizing enzymes and transporters using human liver microsomes, cryopreserved human hepatocytes, and transporter-overexpressed cells were negative. IMPLICATIONS: Red ginseng poses minimal risks for clinically relevant CYP- or OATP-mediated drug interactions and is well tolerated. Clinical Research Information Service registry no.