Clopidogrel transfer into human milk: case series - a contribution from the ConcePTION project.

Introduction: Implementation of breastfeeding recommendations is hampered by-among others-lacking information regarding medicine safety during breastfeeding. This article describes the clinical and pharmacokinetic data of breastfeeding mothers using clopidogrel (CLP) as secondary prevention following (suspicion of) a cerebrovascular accident.

Methods: A 29-year-old and 42-year-old woman were chronically treated with 75 mg CLP once daily.

In vitro-in silico analysis reveals that loss of tankyrase1/2 improves bile acid handling in genetically engineered HepG2 cultures.

Modelling and simulation of hepatic bile acids (BA) kinetics is instrumental to understand mechanisms underlying drug-induced cholestasis (DiCho). A recent study has shown that the loss of tankyrase1/2 (TNKS1/2) matured the hepatic phenotype in vitro in terms of cellular respiration rate and metabolism. However, whether this phenotype was accompanied with more in vivo relevant hepatic BA handling was not investigated.

In Vitro-In Silico Models to Elucidate Mechanisms of Bile Acid Disposition and Cellular Aerobics in Human Hepatocytes.

Understanding the kinetics of hepatic processes, such as bile acid (BA) handling and cellular aerobic metabolism, is crucial for advancing our knowledge of liver toxicity, particularly drug-induced cholestasis (DiCho). This article aimed to construct interpretable models with parameter estimations serving as reference values when investigating these cell metrics. Longitudinal datasets on BA disposition and oxygen consumption rates were collected using sandwich-cultured human hepatocytes.

β-D-N-hydroxycytidine (NHC, EIDD-1931) inhibits chikungunya virus replication in mosquito cells and ex vivo Aedes aegypti guts, but not when ingested during blood-feeding.

Chikungunya virus (CHIKV) is a mosquito-borne virus transmitted by Aedes mosquitoes. While there are no antiviral therapies currently available to treat CHIKV infections, several licensed oral drugs have shown significant anti-CHIKV activity in cells and in mouse models. However, the efficacy in mosquitoes has not yet been assessed.

Effect of sleeve gastrectomy and Roux-en-Y gastric bypass on gastrointestinal physiology.

Background: Knowledge regarding the gastrointestinal physiology after sleeve gastrectomy and Roux-en-Y gastric bypass is urgently needed to understand, prevent and treat the nutritional and pharmacological complications of bariatric surgery.

Aim: To investigate the effect of sleeve gastrectomy and Roux-en-Y gastric bypass on gastrointestinal motility (e.g.

Investigating the Mechanisms behind the Positive Food Effect of Abiraterone Acetate: In Vitro and Rat In Situ Studies.

The anticancer agent abiraterone suffers from an extensive positive food effect after oral intake of the prodrug abiraterone acetate (Zytiga). The underlying processes determining postprandial abiraterone absorption were investigated in this study. The impact of lipids and lipid digestion products on (i) the solubility of abiraterone acetate and abiraterone, (ii) the conversion of abiraterone acetate to abiraterone, and (iii) the passive permeation of abiraterone was determined in vitro.

Orlistat disposition in the human jejunum and the effect of lipolysis inhibition on bile salt concentrations and composition.

The lipolysis-mediated postprandial small intestinal environment is known to influence the solubilisation and subsequent absorption of lipophilic drugs. In a previously performed small-scale clinical study in healthy volunteers, co-administration of the lipase inhibitor orlistat increased jejunal solubilisation and systemic absorption of fenofibrate after intake of the lipid-based formulation Fenogal. In the present study, the jejunal disposition of the locally acting orlistat was assessed and linked to fenofibrate solubilisation.

HIV protease inhibitors Nelfinavir and Lopinavir/Ritonavir markedly improve lung pathology in SARS-CoV-2-infected Syrian hamsters despite lack of an antiviral effect.

Nelfinavir is an HIV protease inhibitor that has been widely prescribed as a component of highly active antiretroviral therapy, and has been reported to exert in vitro antiviral activity against SARS-CoV-2. We here assessed the effect of Nelfinavir in a SARS-CoV-2 infection model in hamsters. Despite the fact that Nelfinavir, [50 mg/kg twice daily (BID) for four consecutive days], did not reduce viral RNA load and infectious virus titres in the lung of infected animals, treatment resulted in a substantial improvement of SARS-CoV-2-induced lung pathology.

The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern.

There is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a potent inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally and that is in clinical development. We here report that PF-332 exerts equipotent in vitro activity against the four SARS-CoV-2 variants of concerns (VoC) and that it can completely arrest replication of the alpha variant in primary human airway epithelial cells grown at the air-liquid interface.

Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia.

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing.

The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model.

Background: Favipiravir and Molnupiravir, orally available antivirals, have been reported to exert antiviral activity against SARS-CoV-2. First efficacy data have been recently reported in COVID-19 patients.

Methods: We here report on the combined antiviral effect of both drugs in a SARS-CoV-2 Syrian hamster infection model.

Chloroquine, an Anti-Malaria Drug as Effective Prevention for Hantavirus Infections.

We investigated whether chloroquine can prevent hantavirus infection and disease and , using the Hantaan virus newborn C57BL/6 mice model and the Syrian hamster model for Andes virus. antiviral experiments were performed using Vero E6 cells, and Old World and New World hantavirus species. Hantavirus RNA was detected using quantitative RT-PCR.

Correction: López-Yerena, A., et al. "Absorption and Intestinal Metabolic Profile of Oleocanthal in Rats" 2020, , 134.

The authors would like to make the following corrections to this paper [...

Reply to "Comment on López-Yerena et al. 'Absorption and Intestinal Metabolic Profile of Oleocanthal in Rats' 2020, , 134".

Recently, in February 2020, we published a study exploring the intestinal absorption and metabolism of oleocanthal (OLC) in rats. A single-pass intestinal perfusion technique (SPIP) was used, involving simultaneous sampling from the luminal perfusate and mesenteric blood. Later, comments on our published paper were released, requesting clarification of specific data.

Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia.

Background & Aims: Despite the growing recognition of duodenal alterations in the pathophysiology of functional dyspepsia (FD), the effect and mechanism of proton pump inhibitors (PPIs) or first-line therapy remain unclear. We studied duodenal and systemic alterations in relation to PPI therapy in patients with FD and healthy volunteers (HVs).

Methods: We performed a prospective interventional study assessing symptoms (Patient Assessment of Gastrointestinal Symptom Severity Index), duodenal alterations, and systemic factors in patients with FD ("FD-starters") and HVs before and after PPI therapy (pantoprazole 40 mg once daily for 4 weeks).

Codeine induces increased resistance at the esophagogastric junction but has no effect on motility and bolus flow in the pharynx and upper esophageal sphincter in healthy volunteers: A randomized, double-blind, placebo-controlled, cross-over trial.

Background: Chronic opioid use can induce esophageal dysfunction with symptoms resembling achalasia and a manometric pattern of esophagogastric junction-outflow obstruction (EGJ-OO). However, the effect of opioids in acute setting on pharyngeal function and esophageal body contractility has not been investigated.

Methods: After positioning the high-resolution impedance manometry (HRiM) catheter, codeine (60 mg) or placebo (glucose syrup) was infused intragastrically.

Exploring the impact of real-life dosing conditions on intraluminal and systemic concentrations of atazanavir in parallel with gastric motility recording in healthy subjects.

This work strived to explore gastrointestinal (GI) dissolution, supersaturation and precipitation of the weakly basic drug atazanavir in humans under different 'real-life' intake conditions. The impact of GI pH and motility on these processes was thoroughly explored. In a cross-over study, atazanavir (Reyataz®) was orally administered to 5 healthy subjects with (i) a glass of water, (ii) a glass of Coca-Cola® and (iii) a glass of water under hypochlorhydric conditions (induced by concomitant intake of a proton-pump inhibitor (PPI)).

Absorption and Intestinal Metabolic Profile of Oleocanthal in Rats.

Oleocanthal (OLC), a phenolic compound of extra virgin olive oil (EVOO), has emerged as a potential therapeutic agent against a variety of diseases due to its anti-inflammatory activity. The aim of the present study is to explore its in vivo intestinal absorption and metabolism. An in situ perfusion technique in rats was used, involving simultaneous sampling from the luminal perfusate and mesenteric blood.

Codeine delays gastric emptying through inhibition of gastric motility as assessed with a novel diagnostic intragastric balloon catheter.

Background: The use of opioids as analgesic is on the rise, despite their inhibitory effect on gastric emptying. A novel feeding catheter with integrated intragastric balloon was developed to continuously assess gastric motility, enabling to investigate the effect of opioids on motility and emptying simultaneously. We aimed to discriminate normal and pharmacologically impaired gastric motility and its impact on gastric emptying in healthy adults.

Exploring gastric drug absorption in fasted and fed state rats.

The small intestine is generally considered the major site of absorption after oral drug administration. Absorption from the stomach is often disregarded, though passive diffusion across the gastric mucosal barrier is theoretically possible. In this study, an in situ gastric bolus administration model was used to study the gastric absorption of pharmaceutical compounds in fasted and fed state rats.

Gastrointestinal and Systemic Disposition of Diclofenac under Fasted and Fed State Conditions Supporting the Evaluation of in Vitro Predictive Tools.

This study aimed to gain further insight into the gastrointestinal disposition of the weakly acidic BCS class II drug diclofenac and the implications for systemic drug exposure in humans under fasted and fed state conditions. For this purpose, gastrointestinal and blood samples were collected from healthy volunteers after oral intake of a commercially available tablet of the potassium salt of diclofenac (i.e.

Gastrointestinal behavior of itraconazole in humans - Part 2: The effect of intraluminal dilution on the performance of a cyclodextrin-based solution.

Hydroxypropyl-β-cyclodextrin (HP-β-CD) is known to enable absorption of the lipophilic drug itraconazole. Since the interaction between HP-β-CD and itraconazole is characterized by a non-lineair, A-type phase-solubility diagram, the present study aimed to investigate the influence of intraluminal dilution (water intake) on the behavior and performance of an orally administered cyclodextrin-based solution of itraconazole. Subsequently, the in vivo behavior was simulated by combining in vitro dilution with permeation assessment.