Imatinib mesylate (GLEEVEC, GLIVEC, formerly STI571) has demonstrated unprecedented efficacy as first-line therapy for treatment all phases of chronic myelogenous leukemia and metastatic unresectable malignant gastrointestinal stromal tumors. Disposition biotransformation imatinib were studied in four male healthy volunteers after a single oral dose 239 mg ¹⁴C-labeled mesylate. Biological fluids analyzed total radioactivity, imatinib, its main metabolite CGP74588. Metabolite...

The purpose of this study was to investigate the absolute bioavailability a single oral dose imatinib (Glivec), 400 mg (capsules vs. solution), compared with imatinib, 100 (intravenous [i.v.] infusion), in healthy subjects. Twelve subjects received treatment each period: 400-mg capsule form or as solution 100-mg i.v. infusion imatinib. Plasma concentrations were measured following treatment; pharmacokinetic parameters and determined. Absolute values (compared infusion) for 98.3% 97.2%,...

Pyroglutamate-amyloid-β (pE-Aβ) peptides are major components of Aβ-oligomers and Aβ-plaques, which regarded as key culprits Alzheimer's disease (AD) pathology. PQ912 is a competitive inhibitor the enzyme glutaminyl cyclase (QC), essential for formation pE-Aβ peptides.A randomized, double-blind, placebo-controlled, single- multiple-ascending oral dose study investigated safety, pharmacokinetics, pharmacodynamics in healthy nonelderly elderly subjects.PQ912 was considered safe well tolerated...

This is the first randomized controlled trial that tests analgesic efficacy of transdermally delivered opioids in healthy volunteers and assesses sensitivity different experimental pain to detect analgesia this setting. Transdermal application full agonist fentanyl (TDF: 12.5 or 25 microg/h) partial buprenorphine (TDB: 35 was compared three models acute (heat pain, painful electrical stimulation, cold pressor) a double-blind, randomized, placebo-controlled, 4-arm crossover study with 20...

KBPA-101 is a human monoclonal antibody of the immunoglobulin M isotype, which directed against O-polysaccharide moiety Pseudomonas aeruginosa serotype O11. This double-blind, dose escalation study evaluated safety and pharmacokinetics in 32 healthy volunteers aged 19 to 46 years. Each subject received single intravenous infusion at 0.1, 0.4, 1.2, or 4 mg/kg body weight placebo infused over 2 h. Plasma samples for pharmacokinetic assessments were taken before as well 0.25, 0.5, 1, 2, 2.5, 4,...

A multiple dose, parallel group study was conducted to assess for a drug-drug interaction between the pyronaridine/artesunate (PA) combination antimalarial and ritonavir. Thirty-four healthy adults were randomized (1:1) receive PA 3 days or with ritonavir (100 mg twice daily 17 days, administered on Days 8–10). Pharmacokinetic parameters pyronaridine, artesunate, its active metabolite dihydroartemisinin (DHA) obtained after last dose 1 10. Ritonavir coadministration did not markedly change...

In a double blind, placebo controlled, cross over study the correlations between single doses (2, 4, and 8 mg), plasma concentrations, antispastic action of tizanidine were investigated in 16 patients with extensor spasticity legs due to multiple sclerosis. An electrogoniometer was used assess muscle tone at knee extensors, applying Wartenberg's pendulum test. Blood samples, clinical assessment by Ashworth scale, strength British Medical Research Council scale obtained concomitantly....

ABSTRACT Finafloxacin is a new fluoroquinolone antibiotic with the unique property of increasing antibacterial activity at pH values lower than neutral. Whereas its neutral matches that other quinolones in clinical use, it expected to surpass this tissues and body fluids acidified by infection or inflammation processes. Pharmacokinetic parameters oral single multiple doses up 800 mg finafloxacin safety/tolerability observations were assessed phase I study including 95 healthy volunteers....

Objective: Establishing local tolerability of transdermal opioid systems is important as more become available for use in a range indications. We compared the skin irritation potential single application fentanyl (Durogesic D-trans; DDTDF) and buprenorphine (Transtec; TDB) patches healthy volunteers. Methods: 46 males females (mean age [range]: 59.6 [50–69] years) with received dose both DDTDF 25 μg/h patch TDB 35 randomised order under naltrexone cover. The incidence severity erythema was...

ABSTRACT The objectives of this study were to characterize any drug-drug interaction between the antimalarial Pyramax (pyronaridine-artesunate [PA]) and CYP2D6 probe substrate metoprolol assess safety 60-day or 90-day PA redosing, particularly with regard liver biochemistry parameters. Healthy adult subjects randomized arm A ( n = 26) B 30), administered 100 mg tartrate in first period, third three daily doses second alone redosing period. received three-day regimen after 60 days...

A double-blind, crossover, placebo-controlled study was carried out in 10 healthy male volunteers to investigate the effects of subcutaneously administered single doses 4 and 8 mg morphine 2.5 5 a new centrally acting analgesic with benzomorphane structure. After an adaptation session, each subject received all five treatments random sequence at intervals 1 week. Quantified EEG, cardiovascular behavioral parameters, quantitative respiratory measurements, body temperature, symptom reports,...

A double-blind, placebo-controlled study was carried out in 10 young healthy volunteers to investigate the effects of single doses 1 and 2 mg guanfacine hydrochloride (Estulic®) 0.15 0.3 clonidine (Catapres®) on electroencephalogram (EEG), subjective mental emotional state, blood pressure heart rate. These are considered be equipotent with regard their antihypertensive effects, as shown long-term therapeutic trials. Each subject received all five treatments random sequence at intervals week....

The effects of training on two memory and attention tasks were investigated in 24 healthy elderly 23 young subjects. Two periods, each consisting four sessions, performed, the assessed during test sessions 1 week thereafter. Significant age-related at pretraining session found for reaction times to a simple visual stimulus, retrieval time information from long-term storage, speed focusing attention. In both age groups, performance first was significantly improved by training; however, effect...

Two double-blind, placebo-controlled studies were carried out at two different centers using the same protocol. Eight young healthy male volunteers recruited for each of studies, which both undertaken to investigate effect single doses 0.6,1.25 and 2.5 mg bromocriptine (Parlodel®) in comparison with 25 50 imipramine (Tofranil®) on electroencephalogram (EEG), subjective mental emotional states, blood pressure, heart rate, plasma prolactin levels. Side effects also noted. The changes resting...

N-terminally truncated and pyroglutamate (pE)-modified Aβ peptides appear to be an important mediator of the Aβ-dependent cytotoxicity occurring in AD. In vivo, formation pE-Aβ is catalyzed by glutaminyl cyclase (QC), suggesting that inhibition QC brain represents new therapeutic target. PQ912 first a series orally available, small molecule inhibitors being developed for treatment Following single multiple dose administration study healthy young subjects (Weber et al, AD/PD 2013), this...