Drug-drug interaction of atazanavir on UGT1A1-mediated glucuronidation of molidustat in human.

Molidustat is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl-hydroxylase enhancing the erythropoietin (EPO) response to HIF; it is in clinical development for the treatment of anaemia related to chronic kidney disease. The predominant role of glucuronidation for molidustat clearance (formation of N-glucuronide metabolite M1) and subsequent renal excretion was confirmed in a human mass balance study, with about 85% of the drug being excreted as M1 in urine. The inhibitory effects of 176 drugs and xenobiotics from various compound classes on the UGT-mediated glucuronidation of molidustat in human liver microsomes (HLMs) were investigated.

Absorption, distribution, metabolism and excretion of molidustat in healthy participants.

The absorption, distribution, metabolism and excretion of molidustat were investigated in healthy male participants. In study 1, a mass balance study, radiolabelled molidustat 25 mg (3.57 MBq) was administered as an oral solution (n = 4).

Effects of oral iron and calcium supplement on the pharmacokinetics and pharmacodynamics of molidustat: an oral HIF-PH inhibitor for the treatment of renal anaemia.

Purpose: The present studies assessed the drug-drug interaction of molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, with iron and calcium supplements, which are common medications in patients with anaemia due to chronic kidney disease (CKD).

Methods: Forty-two healthy men received molidustat alone (fasted or fed) or combined with oral iron(II) or calcium(II), given immediately before or between 4 h before and 1 h after molidustat in three randomized, open-label, crossover studies (12-15 participants per study). Molidustat AUC and C were assessed as the main pharmacokinetic parameters, and endogenous erythropoietin (EPO) was measured to evaluate pharmacodynamics.

Next-Generation DILI Biomarkers: Prioritization of Biomarkers for Qualification and Best Practices for Biospecimen Collection in Drug Development.

The diagnosis and management of drug-induced liver injury (DILI) remains a challenge in clinical trials in drug development. The qualification of emerging biomarkers capable of predicting DILI soon after the initiation of treatment, differentiating DILI from underlying liver disease, identifying the causal entity, and assigning appropriate treatment options after DILI is diagnosed are needed. Qualification efforts have been hindered by lack of properly stored and consented biospecimens that are linked to clinical data relevant to a specific context of use.

Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals With Renal Impairment.

Finerenone (BAY 94-8862) is a nonsteroidal mineralocorticoid receptor antagonist in development for the treatment of diabetic kidney disease. This observational trial compared the pharmacokinetics of a single oral dose of finerenone 10 mg (immediate-release tablet) in adults with mild (creatinine clearance [CL ] 50-80 mL/min; n = 8), moderate (CL 30 to < 50 mL/min; n = 8), or severe (CL < 30 mL/min; n  =  9) renal impairment with those in adults with normal renal function (CL > 80 mL/min; n  = 8) over 96 hours postdose. Exposure to finerenone was not affected by mild renal impairment.

Pharmacokinetics, safety and tolerability of the novel, selective mineralocorticoid receptor antagonist finerenone - results from first-in-man and relative bioavailability studies.

The safety, tolerability and pharmacokinetics of the selective nonsteroidal mineralocorticoid receptor antagonist finerenone were evaluated in healthy male volunteers in two randomized, single-centre studies. Study 1 was a first-in-man, single-blinded, placebo-controlled, parallel-group, dose-escalation study. Fasted participants (n = 45) received single oral doses of finerenone 1-40 mg polyethylene glycol (PEG) solution or placebo.

Creatine phosphokinase elevation in obstructive sleep apnea syndrome: an unknown association?

Study Objectives: To evaluate the impact of obstructive sleep apnea syndrome (OSAS) on serum creatine phosphokinase (CK) levels.

Design: Single-center prospective cross-sectional study.

Setting: Academic sleep disorder center.

Pseudomembranous and obstructive Aspergillus tracheobronchitis - optimal diagnostic strategy and outcome.

Pseudomembranous and obstructive Aspergillus tracheobronchitis (PMATB/OATB) are still considered to be refractory to therapy and to have a fatal outcome. To evaluate the optimal diagnostic strategy and to describe factors affecting the outcome of PMATB and OATB. Retrospective analysis of four new cases of PMATB and OATB combined with 16 previously reported cases over a 10-year period (1995-2004).

[A case of arteria cerebri aneurysm, sepsis, and miliary lung infiltrates in a 32-year-old woman].

Background: Miliary tuberculosis is a rare manifestation of tuberculosis with a high mortality rate. Diagnosis may easily be missed when severe neurologic symptoms are the first clinical manifestation. A typical case of miliary tuberculosis is reported, with special regard to the problems of diagnostic work-up.