Utility of a single adjusting compartment: a novel methodology for whole body physiologically-based pharmacokinetic modelling

<p>Abstract</p> <p>Background</p> <p>There are various methods for predicting human pharmacokinetics. Among these, a whole body physiologically-based pharmacokinetic (WBPBPK) model is useful because it gives a mechanistic description. However, WBPBPK models cannot predict human pharmacokinetics with enough precision. This study was conducted to elucidate the primary reason for poor predictions by WBPBPK models, and to enable better predictions to be made without reliance on complex concepts.</p> <p>Methods</p> <p>The primary reasons for poor predictions of human pharmacokinetics were investigated using a generic WBPBPK model that incorporated a single adjusting compartment (SAC), a virtual organ compartment with physiological parameters that can be adjusted arbitrarily. The blood flow rate, organ volume, and the steady state tissue-plasma partition coefficient of a SAC were calculated to fit simulated to observed pharmacokinetics in the rat. The adjusted SAC parameters were fixed and scaled up to the human using a newly developed equation. Using the scaled-up SAC parameters, human pharmacokinetics were simulated and each pharmacokinetic parameter was calculated. These simulated parameters were compared to the observed data. Simulations were performed to confirm the relationship between the precision of prediction and the number of tissue compartments, including a SAC.</p> <p>Results</p> <p>Increasing the number of tissue compartments led to an improvement of the average-fold error (AFE) of total body clearances (CL_tot) and half-lives (T_1/2) calculated from the simulated human blood concentrations of 14 drugs. The presence of a SAC also improved the AFE values of a ten-organ model from 6.74 to 1.56 in CL_tot, and from 4.74 to 1.48 in T_1/2. Moreover, the within-2-fold errors were improved in all models; incorporating a SAC gave results from 0 to 79% in CL_tot, and from 14 to 93% in T_1/2of the ten-organ model.</p> <p>Conclusion</p> <p>By using a SAC in this study, we were able to show that poor prediction resulted mainly from such physiological factors as organ blood flow rate and organ volume, which were not satisfactorily accounted for in previous WBPBPK models. The SAC also improved precision in the prediction of human pharmacokinetics. This finding showed that the methodology of our study may be useful for functionally reinforcing a WBPBPK model.</p

Testing Lorentz Invariance with a Double-Pass Optical Ring Cavity

We have developed an apparatus to test Lorentz invariance in the photon sector by measuring the resonant frequency difference between two counterpropagating directions of an asymmetric optical ring cavity using a double-pass configuration. No significant evidence for the violation was found at the level of $\delta c /c \lesssim 10^{-14}$. Details of our apparatus and recent results are presented.Comment: 4 pages, 1 figure. Presented at the Sixth Meeting on CPT and Lorentz Symmetry, Bloomington, Indiana, June 17-21, 201

Effect of Specimen Size on Toughness Evaluation by Charpy Test

Herein we present an experimental investigation on the toughness evaluation method for the samples of copper and aluminum, which are generally employed as electronic equipment parts, through the miniaturized version of the Charpy impact test. Overall, the resulting high reproducibility of the absorbed energy values informed by the miniaturized Charpy impact test can be witnessed; moreover, it is possible to compare the values given by the Japanese industrial standard (JIS) Charpy impact test to those given by the miniaturized Charpy impact test and correction factors were calculated accordingly

Upper Limit on Gravitational Wave Backgrounds at 0.2 Hz with Torsion-bar Antenna

We present the first upper limit on gravitational wave (GW) backgrounds at an unexplored frequency of 0.2 Hz using a torsion-bar antenna (TOBA). A TOBA was proposed to search for low-frequency GWs. We have developed a small-scaled TOBA and successfully found {\Omega}gw(f) < 4.3 \times 1017 at 0.2 Hz as demonstration of the TOBA's capabilities, where {\Omega}gw (f) is the GW energy density per logarithmic frequency interval in units of the closure density. Our result is the first nonintegrated limit to bridge the gap between the LIGO band (around 100 Hz) and the Cassini band (10-6 - 10-4 Hz).Comment: 4 pages, 5 figure

EFFECTS OF VARIOUS BIOMECHANICAL ERRORS ON COMPUTED JOINT KINETICS VALUES

Inverse dynamics analysis has been widely used to evaluate the joint kinetics during various human movements. Several investigators have reported that the joint kinetic computations could be considerably affected by diverse biomechanical errors. Kim et al (2007) clarified the influence of measurement errors of Center of Pressure (CoP) location of force platform on calculated three-dimensional (3D) lower limb joint moment during walking. However, it is not yet clear how biomechanical errors, such as errors in CoP, Body Segment Parameters (BSP) and Joint Center Location (JCL) data, affect the calculated joint kinetics values. The purpose of this study was to clarify the influences of the alterations of anthropometric, kinematic, and kinetic variables on the magnitude and time-series curve patterns of the 3D ankle joint moment during human running

Started Activities of 80-Year-Old Japanese Seniors

18th ISA World Congress of Sociolog