• East Asian mathematical journal
• /
• v.36 no.1
• /
• pp.81-90
• /
• 2020

Many compartment models assume a kinetically homogeneous amount of materials that have well-stirred compartments. However, based on observations from such processes, they have been heuristically fitted by exponential or gamma distributions even though biological media are inhomogeneous in real environments. Fractional differential equations using a specific kernel in Pharmacokinetic/Pharmacodynamic (PKPD) model are recently introduced to account for abnormal drug disposition. We discuss a tumor growth inhibition (TGI) model using fractional-order derivative from it. This represents a tumor growth delay by cytotoxic agents and additionally show variations in the equilibrium points by the change of fractional order. The result indicates that the equilibrium depends on the tumor size as well as a change of the fractional order. We find that the smaller the fractional order, the smaller the equilibrium value. However, a difference of them is the number of concavities and this indicates that TGI over time profile for fitting or prediction should be determined properly either fractional order or tumor sizes according to the number of concavities shown in experimental data.

• The Korean Journal of Pharmacology
• /
• v.31 no.2
• /
• pp.251-259
• /
• 1995

Pharmacokinetics and pharmacodynamics of metoprolol, a selective beta-l blocker, were examined for 360 minutes after intravenous bolus administration of metoprolol to 6 dogs. Plasma concentration and excreted amount in the urine metoprolol were measured by liquid chromatography with fluorescence detection. PR interval and heart rate were measured by ECG monitoring. Blood pressure was monitored through intraarterial catheter in femoral artery and cardiac output by thermodilution method using Swan-Ganz catheter. To analyze the effect site concentration-response relationship, plasma concentration and pharmacological effects were simultaneously fitted to a two pharmacokinetic compartment linked to pharmacodynamic model with NONLIN program. Results are as follows. 1) The plasma concentration of metoprolol after intrvenous injection decreased biexponentially. The terminal half-life estimated was $1.33{\pm}0.40$ hours and the volume of distribution at steady state (Vdss) and the total body clearance were $1.04{\pm}0.4\;L/kg,\;6.55{\pm}2.21\;L/hr$, respectively. The central compartment volume of distribution and peripheral compartment volume of distribution were $0.35{\pm}0.14L/kg\;and\;0.69{\pm}0.34L/kg$. The renal clearance and intercompartment clearance were $0.53{\pm}0.25\;L/min\;and\;0.35{\pm}0.19\;L/min$. 2) Simulated biophase concentration-response curve shows hyperbolic relationship and the estimated concentration-effect relationship was best explained by Emax model when the prolongation of PR interval and the reduction of the heart rate were used as pharmacodynamic parameters. Emax and EC50 were estimated to be $26.3{\pm}4.7\;msec\;and\;88.8{\pm}82.3\;g/ml$ for PR interval, and $48.7{\pm}18.8\;beats/min\;and\;113.5{\pm}78.7\;ng/ml$ for heart rate, respectively. 3) The changes of cardiac output-effect site concentration relationship was best fitted by a linear model and the slope of the relationship was $0.005{\pm}0.003$. Diastolic blood pressure-effect site concentration relationship was also explained by the linear model and the slope of the relationship was $0.038{\pm}0.034$.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.17 no.4
• /
• pp.930-938
• /
• 2003

The purpose of the present study was to investigate the effects of Hyunhosaiksan (HHS) on antithrombotic actions which include blood activation, thrombus removal, warming of circulating blood, and the control of pain on abdomen and lower and upper burning spaces. HHS significantly inhibited platelet aggregation induced by ADP and epinephrine in a HHS dose-dependent manner when analyzed by the Sigmoid Emax model in WinNonlin. EC50 values of HHS were 1.71 ㎍/ml and 0.004 ㎍/ml for ADP and epinephrine respectively. In the vivo study, HHS inhibited pulmonary embolism induced by collagen and epinephrine, which was however statistically insignificant. HHS increased number of platelets, APTT and volume of fibrinogen significantly as compared with the control group in dextran-induced thrombus model. Furthermore, HHS stimulated levels of blood flow in vivo though its effect was not observed in vitro. These results suggest that Hyunhosaiksan (HHS) can be used for treating numerous diseases related with blood aggregation and circulation problems. Further systematic investigations on the synergic effects among drugs used in the oriental medicine as well as in the western medicine in relation to thrombosis therapy would provide an important insight into the potential therapeutic applications.

• The Journal of Advanced Prosthodontics
• /
• v.12 no.3
• /
• pp.173-180
• /
• 2020

PURPOSE. This study compared digital (reference point matching) and replica methods for measuring marginal and internal fit of full coverage restorations. MATERIALS AND METHODS. A maxillary left first molar typodent was fixed on to an aluminum base and prepared to receive all-ceramic full coverage restoration. The model was scanned with an intraoral scanner (CEREC Omnicam, Sirona, York, PA, USA). Twelve crowns were fabricated from lithium disilicate blocks (IPS emax CAD, Ivoclar Vivadent) and then crystalized. Marginal and internal fit of each restoration was measured by two examiners using replica and a new digital three-dimensional technique. Reliability between the two methods and two examiners was assessed by correlation and Cronbach's Alpha coefficient (P<.05). A Bland-Altman assessment for agreement was used to compare the two methods. RESULTS. Bland-Altman assessment showed that the mean of difference for marginal, absolute marginal, and axial gap was respectively -1.04 ㎛, -41.9 ㎛, and -29.53 ㎛ with limit of agreement (LOA) between -37.26 to 35.18 ㎛ for marginal, -105.85 to 22.05 ㎛ for absolute marginal and -80.52 to 22.02 ㎛ for axial gap. Positive correlation for repeatability (P<.05) in determining marginal and internal gaps by the two examiners in both techniques was revealed. Reliability of both techniques in all sites of measurements was at least good (0.8 ≤ α < 0.9). CONCLUSION. Both measuring techniques appeared highly reliable for evaluating fit of fixed dental restorations, while reference point matching provided higher values in axial and absolute marginal gap assessment.

• The Korean Journal of Nuclear Medicine
• /
• v.37 no.6
• /
• pp.355-363
• /
• 2003

Purpose: Regional contractility can be calculated using the regional volume change of left ventricle measured by gated myocardial SPECT image and curve of central artery pressure obtained from radial artery pressure data. In this study, a program to obtain the regional contractility was developed, and reproducibility of regional contractility measurement was assessed. Materials and Methods: Seven patients(male:female=5:2, $58{\pm}11.9$ years) with coronary artery diseases underwent gated Tc-99m MIBI myocardial SPECT twice without delay between two scans. Regional volume change of left ventricle was estimated using CSA (Cardiac SPECT Analyzer) software developed in this study. Regional contractility was iteratively estimated from the time-elastance curve obtained using the time-pressure curve and regional time-volume curve. Reproducibility of regional contractility measurement assessed by comparing the contractility values measured twice from the same SPECT data and by comparing those measured from the pair of SPECT data obtained from a same patient. Results: Measured regional contractility was $3.36{\pm}3.38{mm}Hg/mL$ using 15-segment model, $3.16{\pm}2.25{mm}Hg/mL$ using 7-segment model, and $3.11{\pm}2.57{mm}Hg/mL$ using 5-segment model. The harmonic average of regional contractility value was almost identical to the global contractility. Correlation coefficient of regional contractility values measured twice from the same data was greater than 0.97 for all models, and two standard deviations of contractility difference on Bland Altman plot were 1.5%, 1.0%, and 0.9% for 15-, 7-, and 5-segment models, respectively. Correlation coefficient of regional contractility values measured from the pair of SPECT data obtained from a same patient was greater than 0.95 for all models, and two standard deviations on Bland Altman plot were 2.2%, 1.0%, and 1.2%. Conclusion: Regional contractility of left ventricle measured using developed software in this study was reproducible. Regional contractility of left ventricle will be a new useful index for myocardial function after analysis of the clinical data.