Search results for "Kinetics"
showing 10 items of 2224 documents
First-in-Human Phase I Study of Lumretuzumab, a Glycoengineered Humanized Anti-HER3 Monoclonal Antibody, in Patients with Metastatic or Advanced HER3…
2016
Abstract Purpose: A first-in-human phase I study was conducted to characterize safety, efficacy, and pharmacokinetic (PK) and pharmacodynamic (PD) properties of lumretuzumab, a humanized and glycoengineered anti-HER3 monoclonal antibody, in patients with advanced cancer. Experimental Design: Twenty-five patients with histologically confirmed HER3-expressing tumors received lumretuzumab (100, 200, 400, 800, 1,600, and 2,000 mg) every two weeks (q2w) in 3+3 dose-escalation phase. In addition, 22 patients were enrolled into an extension cohort at 2,000 mg q2w. Results: There were no dose-limiting toxicities. Common adverse events (any grade) included diarrhea (22 patients, 46.8%), fatigue (21 …
Effect of single-dose and short-term administration of quercetin on the pharmacokinetics of talinolol in humans – Implications for the evaluation of …
2013
Quercetin has been shown to inhibit intestinal P-glycoprotein-mediated drug efflux. A crossover clinical study was performed in 10 healthy volunteers to assess the effect of single-dose and repeated quercetin intake on the pharmacokinetics of talinolol, a substrate of intestinal P-glycoprotein. Unexpectedly, mean area under the plasma concentration-time curve (AUC0-48h) and maximal plasma concentration (cmax) were slightly decreased following concomitant and short-term quercetin administration (3186.0 versus 2468.3 and 2527.7 ng h/ml, p>0.05; 309.7 versus 212.0 and 280.6 ng/ml, p>0.05). Individual analysis revealed that talinolol AUC0-48h was lowered by 23.9% up to 60.6% in 5 subjects and c…
Effects of controlled-release on the pharmacokinetics and absorption characteristics of a compound undergoing intestinal efflux in humans
2006
Abstract Objective The number of active pharmaceutical ingredients (API) undergoing inhibitable and saturable intestinal efflux is considerable. As a consequence, absorption and bioavailability may depend on the intestinal concentration profile of the drug and may vary as a function of dose and release rate of the drug from the dosage form. The impact of controlled versus immediate-release on the absorption of P-glycoprotein substrates is currently unknown. Thus, the main focus of the present study was a comparison of the pharmacokinetics of the P-gp model substrate talinolol following administration of immediate-release (IR) and controlled-release (CR) tablets to healthy human volunteers w…
Dynamics of cytomegalovirus (CMV) plasma DNAemia in initial and recurrent episodes of active CMV infection in the allogeneic stem cell transplantatio…
2011
Preemptive antiviral therapy strategies for active cytomegalovirus (CMV) infection occurring in allogeneic stem cell transplant recipients should be optimized to avoid overtreatment. The current study was aimed at determining whether the analysis of the kinetics of CMV DNA load in plasma may provide useful information for the therapeutic management of active CMV infection in this setting. A total of 59 consecutive patients were included in the study, of which 40 (67.8%) developed 1 (n = 21) or more (n = 19) episodes of CMV DNAemia. The need for antiviral therapy for initial or secondary episodes of CMV DNAemia could not be predicted on the basis of the CMV DNA load value in the first plasma…
Pharmacokinetic Interactions of Clozapine With Selective Serotonin Reuptake Inhibitors
1998
Pharmacokinetic interactions of clozapine and its metabolites N-desmethylclozapine and clozapine N-oxide with the selective serotonin reuptake inhibitors (SSRIs) fluvoxamine and paroxetine were investigated in a prospective study in schizophrenic patients under steady-state conditions. Thirty patients were treated with clozapine at a target dose of 2.5 to 3.0 mg/kg of body weight. After gradual dose escalation, serum concentrations of clozapine and two metabolites were determined twice at 7-day intervals after steady-state conditions had been reached. Then, fluvoxamine (50 mg/day) or paroxetine (20 mg/day) was added in 16 and 14 patients, respectively. Serum concentrations of clozapine and …
Peginterferon-Α_2B plus ribavirin is more effective than peginterferon-Α_2A plus ribavirin in menopausal women with chronic hepatitis C.
2012
Under-enrolment of women to randomized clinical trials, including chronic hepatitis C, has long been recognized. The aim of this study was to identify factors predictive of sustained virological response (SVR) to PEG IFN/Ribavirin antiviral therapy in relation to gender and reproductive status of female patients involved. Seven hundred and forty-six treatment-naïve patients (431 men, 315 women) treated with Peg-IFNα-2a (180 μg/week) or Peg-IFNα-2b (1.5 μg/kg/week) plus ribavirin (800–1400 mg/day) for 24 or 48 weeks were studied between 2006 and 2010. Differences in SVR rate, overall and by gender were assessed after adjustment and propensity score matching. SVR was obtained in 44.2% of Peg-…
Dose-dependent absorption and elimination of cefadroxil in man.
1991
The pharmacokinetic behaviour of cefadroxil was dose-dependent in healthy male volunteers following the oral administration of single doses of 5, 15, and 30 mg.kg-1. As the dose of cefadroxil increased from 5 to 15 and 30 mg.kg-1, the peak plasma concentrations, normalized to 5 mg.kg-1, decreased significantly from 15.1 to 10.7 and 7.6 mg.l-1, while the corresponding normalized areas under the plasma concentration-time curves from 0 to 2 h decreased significantly from 1258 to 946 and 801 min.mg.l-1. When the same subjects were given 5 mg.kg-1 of cefadroxil together with 45 mg.kg-1 of cephalexin, the absorption of cefadroxil was slowed to a similar or greater extent than with the high dose o…
Histological and fine structural features of pancreatic ductal adenocarcinomas in relation to growth and prognosis: studies in xenografted tumours an…
1985
Histology and fine structure of pancreatic ductal adenocarcinomas were assessed with respect to their significance for tumour growth and prognosis. The histological parameters included glandular differentiation, nuclear anaplasia, nuclear size, and mitotic activity (number of mitoses per high power field). Using these criteria three grades of malignancy were distinguished. They correlated well with the growth kinetics of seven human pancreatic ductal adenocarcinomas transplanted into nude mice. The tumour doubling time of a G 3 carcinoma was about half that of a G 1 carcinoma. On electron microscopy the tumour grade was reflected in the degree of functional differentiation of the neoplastic…
Speed of sound measurements in mandibular and phalangeal bone during growth
2001
The micromechanical and elastic properties of bone, its structural maturity and, indirectly, mineral density are important factors for the planning and assessment of orthodontic and/or jaw orthopaedic treatment. This clinical study was undertaken to evaluate age-related changes in the anterior mandibular body. The speed of sound (SOS) has demonstrated age dependency in various peripheral bones and has been proposed as an alternative method for investigating bone parameters without the use of radiation. The ultrasound transmission velocity was measured in 184 healthy subjects (93 females, 91 males; mean age 17.6 +/- 13.7 years). According to the statistical analysis, the data did not reveal …
Busulfan systemic exposure after oral administration of extemporeanously prepared high-dose busulfan capsules.
2009
Purpose. The aim of the study was to analyze patients’ busulfan (BU) exposure after oral administration of extemporeanously prepared BU capsules prior to blood stem cell transplantation. Methods. Patients were treated with 1 mg/kg body weight BU administered orally every 6h on each of 4 consecutive days prior to blood stem cell transplantation. Each BU dose was administered in 1 gelatine capsule to be swallowed and containing the individually calculated dose of pure BU active substance. Blood samples were obtained from 6 adult patients 0, 30, 60, 90, 120, 180, 240, 300, and 360 min after the 1st, 5th, and 13th BU dose, frozen and analyzed subsequently by using a HPLC assay with UV detectio…