Development of Cilofexor, an intestinally-biased Farnesoid X Receptor agonist, for the treatment of fatty liver disease.

The farnesoid X receptor (FXR) is a nuclear receptor that controls bile acid, lipid, and cholesterol metabolism. FXR-targeted drugs have shown promise in late-stage clinical trials for non-alcoholic steatohepatitis. Herein, we used clinical results from our first non-steroidal FXR agonist, Px-102 (4-[2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methoxy]phenyl]cyclopropyl] benzoic acid), to develop cilofexor, a potent, non-steroidal FXR agonist with a more manageable safety profile.

[Care pathway for Covid-19 patients in a hospital in Luxembourg].

The current care pathway for COVID-19 patients was set up at the Centre Hospitalier de Luxembourg following the experiences of the first wave. The role of the nurse in this pathway is fundamental: she coordinates care and the multidisciplinary team as well as the families, in addition to monitoring and treating the patients. Her tool is clinical reasoning, which is the guarantee of care adapted to the needs and expectations of the patients.

The Non-Steroidal FXR Agonist Cilofexor Improves Portal Hypertension and Reduces Hepatic Fibrosis in a Rat NASH Model.

Background: The farnesoid X receptor (FXR) influences hepatic metabolism, inflammation and liver fibrosis as key components of non-alcoholic steatohepatitis (NASH). We studied the effects of the non-steroidal FXR agonist cilofexor (formerly GS-9674) on portal pressure and fibrosis in experimental NASH.

Methods: NASH was induced in Wistar rats using a choline-deficient high-fat diet plus intraperitoneal sodium nitrite injections.

[Analysis of records and professionalisation of care].

A hospital has initiated a nursing research project to support the nursing teams in their professional development. Record closing, a method involving the critical reading of patients' records when they are discharged, reinforces professional identity and contributes to the development of individual and collective competencies.

The nuclear bile acid receptor FXR controls the liver derived tumor suppressor histidine-rich glycoprotein.

The nuclear bile acid receptor Farnesoid X receptor (FXR) is strongly expressed in liver and intestine, controls bile acid and lipid homeostasis and exerts tumor-protective functions in liver and intestine. Histidine-rich glycoprotein (HRG) is an abundant plasma protein produced by the liver with the proposed function as a pattern recognition molecule involved in the clearance of immune complexes, necrotic cells and pathogens, the modulation of angiogenesis, the normalization of deranged endothelial vessel structure in tumors and tumor suppression. FXR recognition sequences were identified within a human HRG promoter fragment that mediated FXR/FXR-agonist dependent reporter gene activity in vitro.

Fluorescence characteristics and pharmacokinetic properties of a novel self-adhesive 5-ALA patch for photodynamic therapy of actinic keratoses.

Actinic keratosis (AK) can be treated by photodynamic therapy (PDT), which is becoming a well-established tool in dermatology. Normally a precursor of the photosensitiser is applied topically and converted into protoporphyrin IX (PPIX) in the cells. By activating PPIX with light, the dysplastic cells will be destroyed.

Evaluation of the effect of candesartan cilexetil on the steady-state pharmacokinetics of tacrolimus in renal transplant patients.

Background: Candesartan cilexetil is a possible treatment for hypertension in renal allograft recipients. Tacrolimus is widely used as an immunosuppressant following renal transplantation. The aim of this study was to evaluate the effect of multiple doses of candesartan cilexetil on the steady-state pharmacokinetics of tacrolimus.

Relative bioavailability and bioequivalence of a newly developed fixed combination sachet of acetylsalicylic acid and pseudoephedrine compared with a preliminary combination.

Acetylsalicylic acid (ASA) and pseudoephedrine (PSE) are often administered together for the treatment of symptoms of the common cold, i.e., nasal congestion, runny nose, sore throat and headache.

Pharmacokinetic interaction study of a fixed combination of 500 mg acetylsalicylic acid/30 mg pseudoephedrine versus each of the single active ingredients in healthy male volunteers.

Unlabelled: Acetylsalicylic acid (CAS 50-78-2, ASA) and pseudoephedrine (CAS 90-82-4, PSE) both are remedies given together for the treatment of the symptoms of a common cold, i.e. mainly nasal congestion, running nose, sore throat and headache.

Relative bioavailability of imipramine (Tofranil) coated tablets in healthy volunteers.

Objectives: Imipramine is a tricyclic antidepressant drug with a considerable hepatic first-pass metabolism resulting in highly variable pharmacokinetic characteristics and desipramine as active major metabolite. This study describes the bioavailability of 3 formulations of imipramine.

Methods: In a randomized, three-period crossover study, 18 healthy male Caucasian subjects received single oral doses of Tofranil 25, Tofranil mite (10 mg) and an aqueous solution containing 25 mg imipramine-HCl.

Intravesical administration of 5-aminolevulinic acid (5-ALA). Safety and pharmacokinetics of 5-ALA and its metabolite protoporphyrin IX.

Objective: In an open study, the local and systemic side effects and pharmacokinetics of 5-aminolevulinic acid (5-ALA) and the fluorescent metabolite protoporphyrin IX (PPIX) were investigated after intravesical administration for the fluorescent photodetection of superficial bladder carcinoma.

Patients And Methods: In 20 patients with confirmed bladder carcinoma, 5-ALA was introduced into the bladder 2 h (15 patients) and 4 h (5 patients) before an elective endoscopic resection. The 5-ALA and PPIX levels in the plasma were determined before and up to 10 h after application, and in the urine 2 h or 4 h after application.

The alpha-glucosidase inhibitor voglibose (AO-128) does not change pharmacodynamics or pharmacokinetics of warfarin.

Objective: Voglibose is a new and potent inhibitor of alpha-glucosidases and is used for the treatment of diabetes mellitus. Since voglibose increases gastrointestinal motility and could thus affect absorption of concomitantly administered drugs, it was investigated whether or not voglibose modifies the pharmacodynamics and pharmacokinetics of warfarin, an oral anticoagulant frequently used in cardiovascular disorders likely to arise in diabetic patients.

Methods: Twelve healthy male subjects were given individually adjusted doses of warfarin to reduce prothrombin time (Quick's method) to a value of about 30-40% of the normal range within the first 8 days.

Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man.

Objective: Pantoprazole is a selective proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzymes in man. Due to the clinical importance of an interaction with anticoagulants, this study was carried out to investigate the possible influence of pantoprazole on the pharmacodynamics and pharmacokinetics of phenprocoumon.

Methods: Sixteen healthy male subjects were given individually adjusted doses of phenprocoumon to reduce prothrombin time ratio (Quick method) to about 30-40% of normal within the first 5-9 days and to maintain this level.

Relative bioavailability of DL-oxyfedrine HCl after single-dose oral administration of tablets as compared to equimolar solutions.

The pharmacokinetics and comparative bioavailability of oxyfedrine after single-dose oral administration of oxyfedrine*HCl tablets in comparison to an equimolar aqueous solution of oxyfedrine*HCl were investigated in 12 healthy male subjects. Six of them received 96 mg DL-oxyfedrine*HCl as tablets and solution and the remaining 6 subjects received 16 mg DL-oxyfedrine*HCl as tablets and solution in a randomized cross-over design. For evaluation of the relative bioavailability of the tablet formulation, the main metabolite norephedrine (expressed as hydrochloride) was analyzed in plasma for all 12 subjects.

Pharmacokinetics and relative bioavailability after single dose administration of 25 mg ketoprofen solution as compared to tablets.

The relative bioavailability of ketoprofen from a liquid formulation as compared to a tablet formulation as reference after single oral dose administration was investigated in 16 healthy male subjects. The subjects received in a randomized, crossover design during one study period of 5 days 2.5 mg of ketoprofen as tablet or liquid formulation administered as single dose with a washout interval of 48 h.