Exploring the Effect of Esomeprazole on Gastric and Duodenal Fluid Volumes and Absorption of Ritonavir

Proton-pump inhibitors (PPIs), frequently prescribed to lower gastric acid secretion, often exert an effect on the absorption of co-medicated drug products. A previous study showed decreased plasma levels of the lipophilic drug ritonavir after co-administration with the PPI Nexium (40 mg esomeprazole), even though duodenal concentrations were not affected. The present study explored if a PPI-induced decrease in gastrointestinal (GI) fluid volume might contribute to the reduced absorption of ritonavir. In an exploratory cross-over study, five volunteers were given a Norvir tablet (100 mg ritonavir) orally, once without PPI pre-treatment and once after a three-day pre-treatment with the PPI esomeprazole. Blood samples were collected for eight hours to assess ritonavir absorption and magnetic resonance imaging (MRI) was used to determine the gastric and duodenal fluid volumes during the first three hours after administration of the tablet. The results confirmed that PPI intake reduced ritonavir plasma concentrations by 40%. The gastric residual volume and gastric fluid volume decreased by 41% and 44% respectively, while the duodenal fluid volume was reduced by 33%. These data suggest that the PPI esomeprazole lowers the available fluid volume for dissolution, which may limit the amount of ritonavir that can be absorbed. Although additional factors may play a role, the effect of PPI intake on the GI fluid volume should be considered when simulating the absorption of poorly soluble drugs like ritonavir in real-life conditions.

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Pediatric Hyperacute Arterial Ischemic Stroke Pathways at Canadian Tertiary Care Hospitals

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2021.27 ◽

2021 ◽

pp. 1-8

Author(s):

Maria Gladkikh ◽

Hugh J. McMillan ◽

Andrea Andrade ◽

Cyrus Boelman ◽

Ishvinder Bhathal ◽

...

Keyword(s):

Ischemic Stroke ◽

Tertiary Care ◽

Pediatric Stroke ◽

Arterial Ischemic Stroke ◽

Pediatric Hospitals ◽

First Choice ◽

Similarities And Differences ◽

Pre Treatment ◽

Magnetic Resonance Imaging Mri ◽

Iv Tpa

ABSTRACT: Background: Childhood acute arterial ischemic stroke (AIS) is diagnosed at a median of 23 hours post-symptom onset, delaying treatment. Pediatric stroke pathways can expedite diagnosis. Our goal was to understand the similarities and differences between Canadian pediatric stroke protocols with the aim of optimizing AIS management. Methods: We contacted neurologists at all 16 Canadian pediatric hospitals regarding AIS management. Established protocols were analyzed for similarities and differences in eight domains. Results: Response rate was 100%. Seven (44%) centers have an established AIS protocol and two (13%) have a protocol under development. Seven centers do not have a protocol; two redirect patients to adult neurology, five rely on a case-by-case approach for management. Analysis of the seven protocols revealed differences in: 1) IV-tPA dosage: age-dependent 0.75–0.9 mg/kg (N = 1) versus age-independent 0.9 mg/kg (N = 6), with maximum doses of 75 mg (N = 1) or 90 mg (N = 6); 2) IV-tPA lower age cut-off: 2 years (N = 5) versus 3 or 10 years (each N = 1); 3) IV-tPA exclusion criteria: PedNIHSS score <4 (N = 3), <5 (N = 1), <6 (N = 3); 4) first choice of pre-treatment neuroimaging: computed tomography (CT) (N = 3), magnetic resonance imaging (MRI) (N = 2) or either (N = 2); 5) intra-arterial tPA use (N = 3) and; 6) mechanical thrombectomy timeframe: <6 hour (N = 3), <24 hour (N = 2), unspecified (N = 2). Conclusions: Although 44% of Canadian pediatric hospitals have established AIS management pathways, several differences remain among centers. Some criteria (dosage, imaging) reflect adult AIS literature. Canadian expert consensus regarding IV-tPA and endovascular treatment should be established to standardize and implement AIS protocols across Canada.

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Pre-treatment with Curcumin Enhances Plasma Concentrations of Losartan and Its Metabolite EXP3174 in Rats

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.35.145 ◽

2012 ◽

Vol 35 (2) ◽

pp. 145-150 ◽

Cited By ~ 8

Author(s):

An-Chang Liu ◽

Li-Xia Zhao ◽

Jie Xing ◽

Tian Liu ◽

Fu-Ying Du ◽

...

Keyword(s):

Plasma Concentrations ◽

Pre Treatment

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Isavuconazole: Case Report and Pharmacokinetic Considerations

Chemotherapy ◽

10.1159/000494329 ◽

2018 ◽

Vol 63 (5) ◽

pp. 253-256 ◽

Cited By ~ 4

Author(s):

Francesco Marchesi ◽

Corrado Girmenia ◽

Bianca Maria Goffredo ◽

Emanuela Salvatorelli ◽

Atelda Romano ◽

...

Keyword(s):

Lymphoblastic Leukemia ◽

Plasma Concentrations ◽

Real Life ◽

Concomitant Administration ◽

Invasive Fungal Disease ◽

High Plasma ◽

Adult Patients ◽

Therapeutic Drug ◽

Hepatic Toxicity ◽

Maintenance Chemotherapy

Invasive fungal disease (IFD) is one of the major causes of morbidity and mortality in immunocompromised patients. Voriconazole (VCZ) and posaconazole (PCZ) remain the most widely used antifungals for the prophylaxis and treatment of IFD. However, VCZ and PCZ are liable for drug-drug interactions and show a pharmacokinetic variability that requires therapeutic drug monitoring (TDM). Isavuconazole (IVZ) is a newest generation triazole antifungal approved for the treatment of invasive aspergillosis (IA) in adult patients and for the treatment of invasive mucormycosis in adult patients for whom treatment with amphotericin B is inappropriate. In clinical trials, IVZ showed linear pharmacokinetics and little or no evidence for interactions with other drugs. There is only modest evidence on IVZ pharmacokinetics and TDM in real-life settings. Here, we report on IVZ pharmacokinetics in a young adult with Ph chromosome-negative acute lymphoblastic leukemia (ALL) who developed a “probable” IA during induction chemotherapy. The patient was initially treated with VCZ, but she developed a severe hepatic toxicity that was associated to the high plasma levels of VCZ. Therefore, VCZ was discontinued and the patient was switched to IVZ. After a loading dose of IVZ, the patient remained on IVZ for 5 months while also receiving standard maintenance chemotherapy for ALL. At day 65 after the start of IVZ, the patient experienced a significant hepatic toxicity; however, no change in IVZ plasma concentrations was observed in the face of a concomitant administration of many other drugs (cancer drugs, antiemetics, other anti-infectives). Hepatic toxicity resolved after discontinuing maintenance chemotherapy but not IVZ. These results show that (i) IVZ plasma concentrations remained stable throughout and were not affected by concomitant ALL therapy, and (ii) there was no relation between IVZ plasma concentration and hepatic toxicity. Thus, in clinical practice IVZ may not require TDM.

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PRE- AND POSTOPERATIVE IMAGING METHODS IN COLORECTAL CANCER

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/0102-672020180001e1371 ◽

2018 ◽

Vol 31 (2) ◽

Cited By ~ 5

Author(s):

Gleim Dias de SOUZA ◽

Luciana Rodrigues Queiroz SOUZA ◽

Ronaldo Mafia CUENCA ◽

Vinícius Martins VILELA ◽

Bruno Eduardo de Morais SANTOS ◽

...

Keyword(s):

Colorectal Cancer ◽

Tnm Classification ◽

Great Majority ◽

Cancer Staging ◽

Screening Tools ◽

Screening Tests ◽

Surgical Evaluation ◽

Pre Treatment ◽

Magnetic Resonance Imaging Mri ◽

American Society

ABSTRACT Introduction: Among the screening tests for colorectal cancer, colonoscopy is currently considered the most sensitive and specific technique. However, computed tomography colonography (CTC), magnetic resonance imaging (MRI), and transrectal ultrasonography have gained significant ground in the clinical practice of pre-treatment, screening and, more recently, post-treatment and surgical evaluation. Objective: To demonstrate the high accuracy of CT and MRI for pre and postoperative colorectal cancer staging. Methods: Search and analysis of articles in Pubmed, Scielo, Capes Periodicals and American College of Radiology with headings “colorectal cancer” and “colonography”. Weew selected 30 articles that contained radiological descriptions, management or statistical data related to this type of neoplasia. The criteria for radiological diagnosis were the American College of Radiology. Results : The great majority of patients with this subgroup of neoplasia is submitted to surgical procedures with the objective of cure or relief, except those with clinical contraindication. CTC colonography is not the most commonly used technique for screening; however, it is widely used for treatment planning, assessment of the abdomen for local complications or presence of metastasis, and post-surgical evaluation. MRI colonography is an alternative diagnostic method to CT, recommended by the American Society of Gastrointestinal Endoscopy. Although there are still no major studies on the use of MRI for screening, the high resolution examination has now shown good results for the American Joint Committee on Cancer TNM classification. Conclusion: MRI and CT represent the best means for colorectal neoplasm staging. The use of these methods as screening tools becomes beneficial to decrease complications and discomfort related to colonoscopy.

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MRI Virtual Biopsy of T2 Hyperintense Breast Lesions

Journal of Clinical Imaging Science ◽

10.25259/jcis_42_2021 ◽

2021 ◽

Vol 11 ◽

pp. 18

Author(s):

Swati Sharma ◽

Chidi Nwachukwu ◽

Carissa Wieseler ◽

Sherif Elsherif ◽

Haley Letter ◽

...

Keyword(s):

Breast Lesions ◽

Resonance Imaging ◽

Post Contrast ◽

Comprehensive Review ◽

Hyperintense Signal ◽

Mri Features ◽

Malignant Breast ◽

Weighted Magnetic Resonance Imaging ◽

Pre Treatment ◽

Magnetic Resonance Imaging Mri

A wide variety of benign and malignant breast processes may generate hyperintense signal at T2-weighted magnetic resonance imaging (MRI). MRI has been traditionally used in the pre-treatment planning of breast cancer, in assessing treatment response and detecting recurrence. In this comprehensive review, we describe and illustrate the MRI features of a few common and uncommon T2 hyperintense breast lesions, with an emphasis on MRI features that help to characterize lesions based on morphological features, specific appearances on T1-and T2-weighted imaging, and enhancement characteristics on the dynamic post-contrast phase that are either diagnostic or aid in narrowing the differential diagnosis.

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Effect of Gastric Fluid Volume on the In Vitro Dissolution and In Vivo Absorption of BCS Class II Drugs: a Case Study with Nifedipine

The AAPS Journal ◽

10.1208/s12248-016-9918-x ◽

2016 ◽

Vol 18 (4) ◽

pp. 981-988 ◽

Cited By ~ 10

Author(s):

Ahmed M. Nader ◽

Sara K. Quinney ◽

Hala M. Fadda ◽

David R. Foster

Keyword(s):

Class Ii ◽

Gastric Fluid ◽

Fluid Volume ◽

In Vitro Dissolution ◽

Bcs Class Ii ◽

Gastric Fluid Volume ◽

In Vivo Absorption

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Drinking 300 mL of Clear Fluid Two Hours Before Surgery Has No Effect on Gastric Fluid Volume and pH in Fasting and Non-fasting Obese Patients

Survey of Anesthesiology ◽

10.1097/01.sa.0000177170.70004.9f ◽

2005 ◽

Vol 49 (5) ◽

pp. 278-279

Author(s):

&NA;

Keyword(s):

Gastric Fluid ◽

Fluid Volume ◽

Obese Patients ◽

Clear Fluid ◽

Gastric Fluid Volume

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Split-dose bowel preparation for colonoscopy and residual gastric fluid volume: an observational study

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2010.03.1125 ◽

2010 ◽

Vol 72 (3) ◽

pp. 516-522 ◽

Cited By ~ 56

Author(s):

Melanie Huffman ◽

R. Zackary Unger ◽

Chandana Thatikonda ◽

Sable Amstutz ◽

Douglas K. Rex

Keyword(s):

Observational Study ◽

Bowel Preparation ◽

Gastric Fluid ◽

Fluid Volume ◽

Split Dose ◽

Gastric Fluid Volume

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Abstract TP25: Increased Risk for Unfavorable Outcome in Patients with Pre-existing Disability Undergoing Endovascular Therapy

Stroke ◽

10.1161/str.48.suppl_1.tp25 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Ronen R Leker ◽

Pavel Gavriliuc ◽

Nour Eddine Yagmur ◽

John M Gomori ◽

Jose E Cohen

Keyword(s):

Endovascular Therapy ◽

Real Life ◽

Unfavorable Outcome ◽

Stroke Severity ◽

Imaging Data ◽

Anterior Circulation ◽

Poor Outcome ◽

Increased Risk ◽

Degree Of Disability ◽

Pre Treatment

Background and Objectives: Most studies evaluating endovascular therapy (EVT) for stroke only included patients without pre-existing disability. However, in real life many patients have pre-existing disability and whether they can benefit from EVT remains unknown. Methods: Patients with large vessel anterior circulation stroke were prospectively enrolled. Patients with no or mild disability (modified Rankin Scale [mRS] 0-2) were compared with patients presenting with pre-existing moderate disability (mRS≥3). Baseline demographics and risk factors, stroke severity (studied with the National Institutes of Health Stroke Scale [NIHSS]), imaging data including pre-treatment ASPECTS and ASPECTS collateral scores, as well as procedure related variables were accrued. Unfavorable outcome was defined as mRS≥4 at day 90. Results: Out of 100 enrolled patients, 85 had baseline mRS≤2 and 15 had pre-stroke mRS≥3. Patients with pre-existing mRS≥3 were significantly older (79.0±6 vs. 66.6±14, p=0.001) and more often had previous strokes (47% vs. 19%, p=0.04) and ASPECTS≤7 (33% vs. 12%, p=0.03). Patients with mRS≥3 at presentation were more likely to have poor outcome or death (OR 4.4 95%CI 1.3-15.0). Four of the patients with pre-existing moderate disability (27%) maintained their previous degree of disability. On multivariate analysis age (OR 1.1 95%CI 1.1-1.2), admission NIHSS (OR 1.2 95%CI 1-1.3) and complete recanalization (OR 0.2 95%CI 0.04-0.68) remained significant modifiers of poor outcome. Conclusions: Patients with pre-existing moderate disability have higher chances for sustaining unfavorable outcomes despite EVT. Nevertheless, some patients maintain the same level of moderate disability and therefore patients with pre-existing moderate disability should not be excluded from EVT.

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