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Plasma Exposure (plasma + exposure)
Selected AbstractsPharmacokinetics of carisbamate (RWJ-333369) in healthy Japanese and Western subjectsEPILEPSIA, Issue 8 2009Peter Zannikos Summary Purpose:, To compare the pharmacokinetics of carisbamate (RWJ-333369) in healthy Japanese and Western adults, and to comparatively assess carisbamate safety and tolerability between the two populations. Methods:, An open-label study was conducted in 24 Japanese and 24 Caucasian healthy subjects. Subjects received a single oral dose of 250 mg carisbamate on day 1 followed by a 3-day washout period; twice-daily dosing of 250 mg carisbamate on days 5,8; subsequently, 500 mg on days 9,12 and a single dose of 500 mg on day 13. Plasma samples were collected for a pharmacokinetic analysis on days 1, 8, and 13. Plasma and urine samples were analyzed for carisbamate and its urinary metabolites by liquid-chromatography-mass-spectrometry. Results:, Following a single dose, carisbamate Cmax and area under the curve (AUC) geometric mean ratios were 16.4% and 28.8% higher in Japanese than in Caucasians, respectively; these differences were statistically significant and their 90% confidence intervals (CIs) fell outside of the 80,125% limits, which are considered not to be of clinical significance. With dose,body weight normalization, Cmax and AUC were similar in Japanese and Caucasian subjects and the 90% CIs were within the 80,125% boundaries. Carisbamate was well tolerated, and its mean oral clearance and half-life were similar in both groups, ranging from 35.1,41.4 ml/h/kg and 11.5,12.8 h. Discussion:, Carisbamate plasma exposure (AUC) and Cmax in Japanese subjects is ,20,25% higher than in Caucasians due to a higher mg/kg dose. After body weight normalization, carisbamate pharmacokinetics was similar between Japanese and Caucasian subjects following single and multiple dosing, and showed the same dose proportionality. [source] Dietary intake of differently fed salmon: a preliminary study on contaminantsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2006C. Bethune Abstract Background, In a previous study, a group of coronary heart disease (CHD) patients exhibited positive cardioprotective effects of fatty acids derived from a diet of farmed Atlantic salmon fed fish oil (Seierstad et al. 2005). This follow-up study examines these patients for plasma exposure to selected organic and inorganic contaminants found in seafood that may detract from the benefits of eating oily fish. Methods, The study design was from Seierstad et al. (2005), where 58 patients were allocated into three groups consuming 700 g week,1 of differently fed Atlantic salmon (Salmo salar) fillets for 6 weeks: 100% fish oil (FO), 100% rapeseed oil (RO), or 50% of each (FO/RO). Results, Different fillets showed graded levels (FO > FO/RO > RO) of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (DLPCBs), indicator PCBs, polybrominated diphenyl ethers (PBDEs), and arsenic (As). Mercury (Hg) and lead (Pb) levels were similar across the three types of fillets. After 6 weeks of consumption, patient levels of PCDDs, DLPCBs, and PCBs in plasma decreased as the dietary intake of these contaminants increased. Plasma PBDEs only showed increases for the FO patients. Levels of inorganic contaminants in plasma showed only slight changes over the study period. Conclusions, These results show a reduction in the use of marine oils in fish feed reduces organic contaminant levels in farmed salmon while still providing a good dietary source of marine fatty acids. [source] Structure Characterization of HSQ Films for Low Dielectrics Uses D4 as Sacrificial Porous MaterialsJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 6 2007Guiqin Yin Hydrogensilsesquioxane (HSQ) (low- k) films were prepared by spin-on deposition using D4 (octamethyl cyclotetrasiloxane) as a sacrificial porous material. The dielectric constant of silica films significantly changed from 3.0 to 2.2. Fourier transform infrared spectroscopy was used to identify the network structure and cage structure of the Si,O,Si bond and other bonds that may appear. We studied the structural and electrical properties of the spin-coated films prepared by mixing HSQ and D4 films after oxygen plasma exposure for 5 min, and studied the structural recovery of the damage by annealing at 350°C for 1.5 h in a nitrogen (N2) ambient. This structure results in significant lowering of the dielectric constant (k) on annealing at 350°C for 1.5 h in an N2 ambient and improvement in the leakage current density. [source] A novel option for dosing of proton pump inhibitors: dispersion of lansoprazole orally disintegrating tablet in water via oral syringeALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2004D. A. Gremse Summary Background :,A new formulation of lansoprazole, the lansoprazole orally disintegrating tablet, rapidly disintegrates in water eliminating the need for swallowing whole pills. Aim :,To assess the effect that dispersing the lansoprazole orally disintegrating tablet in water would have on lansoprazole pharmacokinetics. Methods :,Forty healthy adult men and women (18,43 years) received two single 15 mg lansoprazole orally disintegrating tablet doses separated by 3 days (one administered directly onto the tongue without water and one dispersed in water and administered orally via syringe) in a randomized, crossover fashion. Serial plasma samples were determined from 0 to 12 h for each dose. Ratios of central values for peak plasma exposure (Cmax) and mean overall extent of exposure (area under the plasma concentration) were used to compare the bioavailability. Results :,The two dosing regimens were bioequivalent, with the point estimate for area under the plasma concentration equalling 1.080 (confidence interval 1.012,1.152) and the point estimate for Cmax equalling 1.082 (confidence interval 0.961,1.218). Conclusions :,Dispersing the 15 mg lansoprazole orally disintegrating tablet in water and administering the dose orally via syringe is bioequivalent to the 15 mg intact lansoprazole orally disintegrating tablet with respect to lansoprazole area under the plasma concentration and Cmax. This dosing route provides an additional, convenient dosing option for lansoprazole. [source] Normally-on/off AlN/GaN high electron mobility transistorsPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 10 2010C. Y. Chang Abstract We report on the novel normally-on/off AlN/GaN high electron mobility transistors (HEMTs) grown by plasma-assisted molecular beam epitaxy. With simple oxygen exposure, the threshold voltage can be tuned from -2.76 V to +1.13 V depending on the treatment time. The gate current was reduced and current-voltage curves show metal-oxide semiconductor diode-like characteristics after oxygen plasma exposure. The extrinsic transconductance of HEMTs decrease with increasing oxygen plasma exposure time due to the thicker Al oxide formed on the gate area. The unity current gain cut-off frequency, fT, and maximum frequency of oscillation, fmax, were 20.4 GHz and 36.5 GHz, respectively for an enhancement-mode HEMT with the gate dimension of 0.4 × 100 ,m2. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Bioavailability of divalproex extended-release formulation relative to the divalproex delayed-release formulationBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 8 2004Sandeep Dutta Abstract Divalproex sodium extended-release tablet (divalproex-ER) is a novel formulation of the conventional divalproex sodium delayed-release tablet (divalproex). In five multiple-dose studies in healthy subjects (n=82) and epilepsy patients (n=86) the estimates of divalproex-ER/divalproex ratios for steady-state 24 h valproic acid area under the curve (AUC) central values, maximum concentration (Cmax) central values and minimum concentration (Cmin) means had ranges of 0.77,0.97, 0.71,0.87 and 0.78,1.03, respectively. These studies used different divalproex regimens (two, three or four times daily) and meal conditions (fasting, low, medium and high calorie meals). Divalproex-ER was administered once daily. A meta-analysis of divalproex-ER/divalproex relative bioavailability across five studies under different meal conditions and divalproex dosing frequencies was performed. This meta-estimate of relative bioavailability was used to provide dosing recommendations for conversion of patients from divalproex to divalproex-ER. The estimated AUC, Cmax and Cmin divalproex-ER/divalproex ratios (95% confidence interval) were 0.89 (0.85,0.94), 0.79 (0.74,0.84) and 0.96 (0.90,1.02), respectively. The food and divalproex regimen had no effect on the relative bioavailability. While switching from divalproex to divalproex-ER, the divalproex-ER daily dose may have to be increased by an average of 12% (calculated as 1.0/0.89) to achieve comparable plasma exposure. Since the divalproex-ER dosage strengths (250 and 500 mg) are not 12% higher than the divalproex dosage strengths (125, 250 and 500 mg), an 8% to 20% higher divalproex-ER daily dose should be considered for conversion from divalproex to divalproex-ER. Copyright © 2004 John Wiley & Sons, Ltd. [source] Surface Science Contribution to the BEN Control on Si(100) and 3C-SiC(100): Towards Ultrathin Nanocrystalline Diamond Films,CHEMICAL VAPOR DEPOSITION, Issue 7-8 2008Jean-Charles Arnault Abstract Deposition of thin and smooth nanocrystalline diamond films requires a high degree of control of the nucleation stage. The nature of the interface between diamond film and substrate is also important for some applications. The successive steps of the bias-enhanced nucleation (BEN) process are studied in-situ on Si(100) and 3C-SiC(100) using electron spectroscopies. Thin nanodiamond films (80,900,nm) have been achieved on Si(100). The formation of a thin covering SiC layer (2,3,nm) during the plasma exposure for parameters stabilization (PEPS) step leads us to study the plasma/surface interactions on 3C-SiC(100) surfaces. The C-terminated 3C-SiC(100) demonstrates a large inertia under microwave plasma (MP)CVD conditions. An enhancement of diamond nucleation on this surface is observed. Moreover, surface analysis reveals very little damage after BEN on 3C-SiC surfaces. [source] Phase I pharmacokinetic study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor vatalanib (PTK787) plus imatinib and hydroxyurea for malignant gliomaCANCER, Issue 10 2009David A. Reardon MD Abstract BACKGROUND: This study determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of the oral vascular endothelial growth factor receptor (VEGFR) inhibitor, vatalanib, when administered with imatinib and hydroxyurea on a continuous daily schedule among recurrent malignant glioma patients. METHODS: All patients received 500 mg of hydroxyurea twice daily. Imatinib was dosed at 400 mg per day for patients not taking enzyme-inducing antiepileptic drugs (EIAEDs; stratum A) and at 500 mg twice-a-day for patients taking EIAEDs (stratum B). Vatalanib was escalated from 500 mg to 1250 mg twice daily in successive cohorts, independently for each stratum. Pharmacokinetics of each drug were assessed. RESULTS: A total of 37 recurrent patients, 34 (92%) with glioblastoma and 3 (8%) with grade 3 malignant glioma, were enrolled. Nineteen patients (51%) were taking EIAEDs. The MTD of vatalanib for all patients was 1000 mg twice-a-day. DLTs were hematologic, gastrointestinal, renal, and hepatic. No patients developed intracranial hemorrhage. Concurrent administration of imatinib and hydroxyurea did not affect vatalanib exposure, but EIAEDs decreased vatalanib and imatinib plasma exposures. CONCLUSIONS: Vatalanib doses up to 1000 mg twice-a-day combined with imatinib and hydroxyurea were well tolerated. Strategies to target tumor blood vessel endothelial cells and pericytes by inhibiting VEGFR and platelet-derived growth factor, respectively, were safe among recurrent malignant glioma patients and may enhance antiangiogenesis activity. Cancer 2009. © 2009 American Cancer Society. [source] | |||||||||||||