The effect of bradykinin 1 receptor antagonist BI 1026706 on pulmonary inflammation after segmental lipopolysaccharide challenge in healthy smokers.

Background: Bradykinin 1 receptor (B1R) signalling pathways may be involved in the inflammatory pathophysiology of chronic obstructive pulmonary disease (COPD). B1R signalling is induced by inflammatory stimuli or tissue injury and leads to activation and increased migration of pro-inflammatory cells. Lipopolysaccharide (LPS) lung challenge in man is an experimental method of exploring inflammation in the lung whereby interference in these pathways can help to assess pharmacologic interventions in COPD.

Pharmacokinetic-Interactions of BI 425809, a Novel Glycine Transporter 1 Inhibitor, With Cytochrome P450 and P-Glycoprotein Substrates: Findings From In Vitro Analyses and an Open-Label, Single-Sequence Phase I Study.

Purpose/background: Glycine transporter-1 inhibitors may ameliorate cognitive deficits in schizophrenia. This study evaluated potential drug-drug interactions with the glycine transporter-1 inhibitor BI 425809.

Methods/procedures: Interactions with cytochromes P450 (CYP) and P-glycoprotein (P-gp) were assessed in in vitro assays using human hepatocytes and Caco-2 cells, respectively.

N -Methylnicotinamide as Biomarker for MATE-Mediated Renal Drug-Drug Interactions: Impact of Cimetidine, Rifampin, Verapamil, and Probenecid.

N -methylnicotinamide (NMN) has been proposed as endogenous biomarker for drug-drug interactions mediated by inhibition of multidrug and toxin extrusion proteins (MATEs) at the renal proximal tubule. We analyzed NMN in plasma and urine samples of two clinical trials investigating a new probe drug cocktail (consisting of digoxin, metformin, furosemide, and rosuvastatin) dedicated to clinically relevant drug transporters. In trial 1, NMN was investigated after single-dose treatment with individual cocktail components or after cocktail treatment.

Validation of a Drug Transporter Probe Cocktail Using the Prototypical Inhibitors Rifampin, Probenecid, Verapamil, and Cimetidine.

Background And Objective: A novel cocktail containing four substrates of key drug transporters was previously optimized to eliminate mutual drug-drug interactions between the probes digoxin (P-glycoprotein substrate), furosemide (organic anion transporter 1/3), metformin (organic cation transporter 2, multidrug and toxin extrusion protein 1/2-K), and rosuvastatin (organic anion transporting polypeptide 1B1/3, breast cancer resistance protein). This clinical trial investigated the effects of four commonly employed drug transporter inhibitors on cocktail drug pharmacokinetics.

Methods: In a randomized open-label crossover trial in 45 healthy male subjects, treatment groups received the cocktail with or without single oral doses of rifampin, verapamil, cimetidine or probenecid.

No relevant pharmacokinetic drug-drug interaction between nintedanib and pirfenidone.

Nintedanib and pirfenidone are approved treatments for idiopathic pulmonary fibrosis (IPF). This open-label, two-group trial investigated the pharmacokinetic drug-drug interaction between these two drugs in patients with IPF.Subjects not treated with antifibrotics at screening (group 1, n=20) received a single nintedanib dose (150 mg) followed by pirfenidone (titrated to 801 mg thrice daily) for 3 weeks, with a further single nintedanib dose (150 mg) on the last day (day 23).

Optimization of a drug transporter probe cocktail: potential screening tool for transporter-mediated drug-drug interactions.

Aims: Previous pharmacokinetic characterization of a transporter probe cocktail containing digoxin (P-gp), furosemide (OAT1, OAT3), metformin (OCT2, MATE1, MATE2-K) and rosuvastatin (OATP1B1, OATP1B3, BCRP) in healthy subjects showed increases in rosuvastatin systemic exposure compared to rosuvastatin alone. In this trial, the doses of metformin and furosemide as putative perpetrators were reduced to eliminate their drug-drug interaction (DDI) with rosuvastatin.

Methods: In a randomized, open-label, single-centre, five-treatment, five-period crossover trial, 30 healthy male subjects received as reference treatments separately 0.

Effects of Metformin and Furosemide on Rosuvastatin Pharmacokinetics in Healthy Volunteers: Implications for Their Use as Probe Drugs in a Transporter Cocktail.

Background: In a recently described probe drug cocktail for clinically relevant drug transporters containing digoxin, furosemide, metformin and rosuvastatin, mutual interactions were essentially absent except for increases in the systemic exposure of rosuvastatin. To optimize the cocktail, we further examined the dose dependence of the effects of metformin and furosemide on rosuvastatin pharmacokinetics.

Methods: This was a randomized, open label, single center, six-treatment, six-period, six-sequence crossover trial.

Relative bioavailability study of linagliptin/metformin tablets in healthy Chinese subjects.

Objective: To evaluate the relative bioavailability of single pill combination (SPC) tablets of linagliptin and metformin compared with separate tablets co-administered in healthy Chinese subjects.

Materials And Methods: This was an open-label, single-dose, randomized, two-period, crossover study in healthy Chinese subjects with two dose groups: linagliptin 2.5 mg/metformin 850 mg and linagliptin 2.

Effect of food and tablet-dissolution characteristics on the bioavailability of linagliptin fixed-dose combination with metformin: evidence from two randomized trials.

Objective: The objectives of the studies reported here were to determine the relative bioavailability of linagliptin and metformin when administered in a fixed-dose combination (FDC) tablet with and without food, and to investigate the relative bioavailability of linagliptin and metformin FDC tablets from two treatment batches with different dissolution behavior.

Methods: These studies were open-label, single-dose, randomized, two-way crossover trials. After an overnight fast, healthy volunteers received an FDC tablet once (with/without food in the food-effect study; or from one of two batches with differing dissolution behavior in the tablet-dissolution study).

Effect of food on the pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, and assessment of dose proportionality in healthy volunteers.

Objectives: Empagliflozin is an orally available, potent and highly selective inhibitor of the sodium glucose cotransporter 2 (SGLT2). This study was undertaken to investigate the effect of food on the pharmacokinetics of 25 mg empagliflozin and to assess dose proportionality between 10 mg and 25 mg empagliflozin under fasted conditions.

Materials And Methods: In this open-label, 3-way, cross-over study, 18 healthy volunteers received 3 single doses of empagliflozin in a randomized sequence (25 mg empagliflozin under fasted conditions, 25 mg empagliflozin after a high-fat, high-calorie breakfast and 10 mg empagliflozin under fasted conditions), each separated by a washout period of at least 7 days.

Training effects of combined resistance and proprioceptive neck muscle exercising.

Objectives: To investigate training effects of two different resistance and proprioceptive exercising concepts of neck muscles.

Material And Method: Twenty-six healthy women participated in a randomized pilot trial. The test persons were randomized to two different neck-training programs (resistance training (RT) and proprioceptive resistance training (PRT)).

The need for pressure changes in CPAP therapy 2-3 months after initial treatment: a prospective trial in 905 patients with sleep-disordered breathing.

Objective: The aim of the study was to investigate the need for pressure change in patients with sleep-disordered breathing (SDB) several weeks after therapy initiation. We prospectively studied 905 consecutive patients (740 men and 165 women) with SDB and therapeutic intervention with continuous positive airway pressure (CPAP)/bilevel PAP.

Methods: Several weeks after therapy initiation, patients were restudied for control, and pressure was optimized if it was necessary.

The weak evidence base for antibiotic prophylaxis in severe acute pancreatitis.

Background/aims: The incidence of acute pancreatitis varies from 5 to 80 per 100,000 inhabitants throughout the world. The most common cause of death in these patients is infection of pancreatic necrosis by enteric bacteria, spurring the discussion of whether or not prophylactic antibiotic administration could be a beneficial approach. We therefore analyzed randomized clinical trials, which form the basis of guidelines and recommendations on this topic.

[(11)C]choline PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy.

Objective: To evaluate [(11)C]choline positron emission tomography/computed tomography ([(11)C]choline PET/CT) for the detection of a biochemical recurrence of prostate cancer after radical prostatectomy.

Methods: Retrospective analysis of [(11)C]choline PET/CT performed in 41 consecutive prostate cancer patients with a rising PSA. The mean time to biochemical relapse was 24 months.

Reliability of a new virtual reality test to measure cervicocephalic kinaesthesia.

The aim of this study was to investigate the cervicocephalic kinaesthesia of healthy subjects for gender and age effects and its reliability in a new virtual reality test procedure. 57 healthy subjects (30 male, 27 females; 18-64 years) were immersed into a virtual 3D scene via a headmounted display, which generated specific head movements. The joint repositioning error was determined in a static and dynamic test at the times T0, T1 (T0+10 minutes) and T2 (T0+24 hours).

Choosing the optimal fit function: comparison of the Akaike information criterion and the F-test.

In many circumstances of data fitting one has to choose the optimal fitting function or model among several alternatives. Criteria or tests on which this decision is based are necessary and have to be well selected. In this preliminary analysis the application of the corrected Akaike information criterion is demonstrated considering the example of determining pharmacokinetic parameters for the blood serum time activity curves of 111In-labeled anti-CD66 antibody.

Evaluation of [11C]-choline positron-emission/computed tomography in patients with increasing prostate-specific antigen levels after primary treatment for prostate cancer.

Objective: To evaluate [(11)C]-choline positron-emission tomography (PET)/computed tomography (CT) for detecting clinical recurrence after primary treatment for prostate cancer.

Patients And Methods: In all, 50 patients with prostate cancer who had had initial therapy (radical prostatectomy in 40, external beam radiation in three and interstitial brachytherapy in seven) had PET/CT using [(11)C]-choline in the presence of an increased or increasing prostate-specific antigen (PSA) level. The mean (range) time to biochemical progression was 22 (2-136) months.

11C-choline positron-emission tomography/computed tomography and transrectal ultrasonography for staging localized prostate cancer.

Objective: To evaluate and compare the role of (11)C-choline positron emission tomography (PET) and transrectal ultrasonography (TRUS) in the preoperative staging of clinically localized prostate cancer.

Patients And Methods: Fifty-five consecutive patients with biopsy-confirmed prostate cancer had TRUS and (11)C-choline PET as a part of their clinical staging programme before radical retropubic prostatectomy (RP). The PET images were prospectively interpreted by a consensus decision of two nuclear medicine physicians and one radiologist with special expertise in the field.

Anti-CD45 monoclonal antibody YAML568: A promising radioimmunoconjugate for targeted therapy of acute leukemia.

Unlabelled: The outcome of hematopoietic cell transplantation for hematologic malignancies may be improved by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the biodistribution of 111In-labeled anti-CD45 antibody in humans using the rat IgG2a monoclonal antibody YAML568 that recognizes a common CD45 epitope present on all human leukocytes.

Methods: Eight patients undergoing bone marrow transplantation received YAML568 labeled with 122 +/- 16 MBq of 111In intravenously followed by serial blood sampling, urine collection, and conjugated view planar gamma-camera imaging up to 144 h after injection.