A drug-drug interaction study and physiologically based pharmacokinetic modelling to assess the effect of an oral 5-lipoxygenase activating protein inhibitor on the pharmacokinetics of oral midazolam.

Aims: Early clinical studies have indicated that the pharmacokinetics of Atuliflapon (AZD5718) are time and dose dependent. The reason(s) for these findings is(are) not fully understood, but pre-clinical profiling suggests that time-dependent CYP3A4 inhibition cannot be excluded. In clinical practice, Atuliflapon will be co-administered with CYP3A4 substrates; thus, it is important to determine the impact of Atuliflapon on the pharmacokinetics (PK) of CYP3A4 substrates.

Examining the consistency in bilingualism and white matter research: A meta-analysis.

This study aimed to systematically investigate the relationship between bilingualism, age, L2 onset age of acquisition (AoA), and white matter integrity (operationalized as fractional anisotropy, FA), addressing inconsistencies in the literature. We conducted a meta-analysis of 23 studies and used meta-regression models to assess the influence of age and L2AoA on effect sizes in studies comparing monolinguals and bilinguals. Even though the overall between-group effect size across the whole brain was unreliable, bilingualism was associated with increased white matter integrity in specific tracts and in groups with a limited range of age and L2AoA.

Design of FLAIR: a Phase 2b Study of the 5-Lipoxygenase Activating Protein Inhibitor AZD5718 in Patients With Proteinuric CKD.

Introduction: Patients with chronic kidney disease (CKD) remain at risk for kidney and cardiovascular events resulting from residual albuminuria, despite available treatments. Leukotrienes are proinflammatory and vasoconstrictive lipid mediators implicated in the etiology of chronic inflammatory diseases. AZD5718 is a potent, selective, and reversible 5-lipoxygenase activating protein (FLAP) inhibitor that suppresses leukotriene production.

Limited sampling strategies for estimation of tacrolimus exposure in kidney transplant recipients receiving extended-release tacrolimus preparation.

Tacrolimus is the key component of most contemporary immunosuppressive drug regimens for the prevention of transplant rejection. Area under the concentration time curve over 24 h (AUC ) predicts efficacy, but predose (trough) tacrolimus blood concentration (C ) is currently used to guide dosing. In clinical or research situations where an estimate of AUC is required, collection of a full 24 h pharmacokinetic (PK) profile is cumbersome.