Validation of Individual Non-Linear Predictive Pharmacokinetic Parameters in a Rabbit Phenytoin Model

Purpose: To evaluate the predictive performance of phenytoin multiple dosing non-linear pharmacokinetic model in rabbits for possible application in therapy individualization in humans.Methods: Phenytoin was intravenously administered to 10 rabbits (2 – 3 kg). Plasma concentrations were measured by high pressure liquid  chromatography (HPLC). Rabbits received 3 single phenytoin doses (11, 22 and 44 mg/kg) and plasma concentrations were fitted according to linear twocompartmental model. In all the rabbits, based on 3 different multiple doses (D1, D2, D3, range 9 – 15 mg/kg), 3 steady state plasma   concentrations (Css1, Css2, Css3, range 20 - 56mg/l) were achieved. Formultiple dosage, the non-linear parameters, Km and Vm, were calculated according to the equations: Km = (D1-D2)/[(D2/Css2)-(D1/Css1)] and Vm = D2+KmD2/Css2, and individually used to calculate Css3 =  D3Km/(Vm-D3). Predicted and measured Css3 values were compared.Results: The values for pharmacokinetic parameters after single doses were dose-dependent. The pronounced inter-individual variations in Km (extreme values 18 – 91 mg/l differed 5.5 times) and Vm (11 – 28  mg/kg/h) values were recorded. Significant correlation of predicted Css3 with the measured value for the same dose (D3) was found (r = 0.854, N = 10, p < 0.01). There was no statistical difference between predicted and measured concentrations (t-dependent test = 1.074, p < 0.05).Conclusion: Non-linear parameters, Km and Vm, obtained from only two steady-state concentration measurements can be successfully used to compute and achieve a particular steady-state plasma concentration and optimal dosage regimen.Keywords: Phenytoin, Rabbit, Pharmacokinetic model, Multiple dosing, Non-linear, Individualizatio

Metal-insulator transition and glassy behavior in two-dimensional electron systems

Studies of low-frequency resistance noise demonstrate that glassy freezing occurs in a two-dimensional electron system in silicon in the vicinity of the metal-insulator transition (MIT). The width of the metallic glass phase, which separates the 2D metal and the (glassy) insulator, depends strongly on disorder, becoming extremely small in high-mobility (low-disorder) samples. The glass transition is manifested by a sudden and dramatic slowing down of the electron dynamics, and by a very abrupt change to the sort of statistics characteristic of complicated multistate systems. In particular, the behavior of the second spectrum, an important fourth-order noise statistic, indicates the presence of long-range correlations between fluctuators in the glassy phase, consistent with the hierarchical picture of glassy dynamics.Comment: Contribution to conference on "Noise as a tool for studying materials" (SPIE), Santa Fe, New Mexico, June 2003; 15 pages, 12 figs. (includes some low-quality figs; send e-mail to get high-quality figs.

Influence of Intra-cell Traffic on the Output Power of Base Station in GSM

In this paper we analyze the influence of intracell traffic in a GSM cell on the base station output power. It is proved that intracell traffic increases this power. If offered traffic is small, the increase of output power is equal to the part of intracell traffic. When the offered traffic and, as the result, call loss increase, the increase of output power becomes less. The results of calculation are verified by the computer simulation of traffic process in the GSM cell. The calculation and the simulation consider the uniform distribution of mobile users in the cell, but the conclusions are of a general nature

The flux ratio of the [OIII] 5007,4959 lines in AGN: Comparison with theoretical calculations

By taking into account relativistic corrections to the magnetic dipole operator, the theoretical [OIII] 5006.843/4958.511 line intensity ratio of 2.98 is obtained. In order to check this new value using AGN spectra we present the measurements of the flux ratio of the [OIII] 4959,5007 emission lines for a sample of 62 AGN, obtained from the Sloan Digital Sky Survey (SDSS) Database and from published observations. We select only high signal-to-noise ratio spectra for which the line shapes of the [OIII] 4959,5007 lines are the same. We obtained an averaged flux ratio of 2.993 +/- 0.014, which is in a good agreement with the theoretical one.Comment: Accepted for publication in the MNRA

Using the Fermilab Proton Source for a Muon to Electron Conversion Experiment

The Fermilab proton source is capable of providing 8 GeV protons for both the future long-baseline neutrino program (NuMI), and for a new program of low energy muon experiments. In particular, if the 8 GeV protons are rebunched and then slowly extracted into an external beamline, the resulting proton beam would be suitable for a muon-to-electron conversion experiment designed to improve on the existing sensitivity by three orders of magnitude. We describe a scheme for the required beam manipulations. The scheme uses the Accumulator for momentum stacking, and the Debuncher for bunching and slow extraction. This would permit simultaneous operation of the muon program with the future NuMI program, delivering 10^20 protons per year at 8 GeV for the muon program at the cost of a modest (~10%) reduction in the protons available to the neutrino program.Comment: 18 pages, 7 figure