• Proceedings of the Safety Management and Science Conference
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• 2009.11a
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• pp.549-555
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• 2009

The research proposes two calculation methods for estimating the overall, within and between standard deviation of population. These standard deviations can be used to evaluate the process capability and performance indexes. The guidelines for using $C_{PK}$ and $P_{PK}$ according to the pattern of common and assignable causes are presented.

• Proceedings of the Korean Society of Toxicology Conference
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• 1998.10a
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• pp.50-50
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• 1998

• Korean Journal of Clinical Pharmacy
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• v.18 no.2
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• pp.84-96
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• 2008

In the recent, pharmacokinetic (PK)/pharmacodynamic (PD) modeling has appeared as a critical path tools in new drug development to optimize drug efficacy and safety. PK/PD modeling is the mathematical approaches of the relationships between PK and PD. This approach in new drug development can be estimated inaccessible PK and PD parameters, evaluated competing hypothesis, and predicted the response under new conditions. Additionally, PK/PD modeling provides the information about systemic conditions for understanding the pharmacology and biology. These advantages of PK/PD model development are to provide the early decision-making information in new drug development process, and to improve the prediction power for the success of clinical trials. The purpose of this review article is to summarize the PK/PD modeling process, and to provide the theoretical and practical information about widely used PK/PD models. This review also provides model schemes and the differential equations for the development of PK/PD model.

• Journal of Life Science
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• v.15 no.3 s.70
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• pp.406-414
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• 2005

The genetic instability of cancer cells may be related to inappropriately activated DNA repair pathways. In present study, the modulated expression of DNA-dependent protein kinase (DNA-PK), a major DNA repair protein, in human cancer metastatic cells was tested. The expressions of Ku70/80, regulatory subunit of DNA-PK, and the Ku DNA-binding activity in various highly metastatic cell lines were higher than those in each parental cell line. Also, the expression of DNA-PKcs, catalytic subunit of DNA-PK, and the kinase activity of the whole DNA-PK complex in highly metastatic cells were significantly increased as compared to those of parental cells, suggesting that the enhanced DNA repair capacity of metastatic cells could be associated with aberrant use of DNA repair, which may mediate tumor progression and metastatic potential. Increased EGFR (epidermal growth factor receptor) signaling has been associated with tumor invasion and metastasis, and the linkage between EGFR-mediated signaling and DNA-PK has been suggested. This study showed that PKI166, the new EGFR tyrosine kinase inhibitor, modulated the expressions of Ku70/80 and DNA-PKcs and also revealed the chemosensitization effect of PKI166 against metastatic cells may be in part due to inhibition of Ku70/80. These results suggest that interference in EGFR signaling by EGFR inhibitor resulted in the impairment of DNA repair activity, and thus DNA-PK could be possible molecular targets for therapy against metastatic cancer cells.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.6
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• pp.733-742
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• 1998

Background: We have previously reported that not only cGMP but also 8-Br-cGMP or 8-pCPT-cGMP, specific and potent stimulators of cGMP-dependent protein kinase (cGMP-PK), increased basal L-type calcium current $(I_{Ca})$ in rabbit ventricular myocytes. Our findings in rabbit ventricular myocytes were entirely different from the earlier findings in different species, suggesting that the activation of cGMP-PK is involved in the facilitation of $I_{Ca}}$ by cGMP. However, there is no direct evidence that cGMP-PK can stimulate $I_{Ca}}$ in rabbit ventricular myocytes. In this report, we focused on the direct effect of cGMP-PK on $I_{Ca}}$ in rabbit ventricular myocytes. Methods and Results: We isolated single ventricular myocytes of rabbit hearts by using enzymatic dissociation. Regulation of $I_{Ca}}$ by cGMP-PK was investigated in rabbit ventricular myocytes using whole-cell voltage clamp method. $I_{Ca}}$ was elicited by a depolarizing pulse to +10 mV from a holding potential of -40 mV. Extracellular 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP), potent stimulator of cGMP-dependent protein kinase (cGMP-PK), increased basal $I_{Ca}}$. cGMP-PK also increased basal $I_{Ca}}$. The stimulation of basal $I_{Ca}}$ by cGMP-PK required both 8-Br-cGMP in low concentration and intracellular ATP to be present. The stimulation of basal $I_{Ca}}$ by cGMP-PK was blocked by heat inactivation of the cGMP-PK and by bath application of 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-pCPT-cGMP), a phosphodiesterase-resistant cGMP-PK inhibitor. When $I_{Ca}}$ was increased by internal application of cGMP-PK, IBMX resulted in an additional stimulation of $I_{Ca}}$. In the presence of cGMP-PK, already increased $I_{Ca}}$ was potentiated by bath application of isoprenaline or forskolin or intracellular application of cAMP. Conclusions: We present evidence that cGMP-PK stimulated basal $I_{Ca}}$ by a direct phosphorylation of L-type calcium channel or associated regulatory protein in rabbit ventricular myocytes.

• Korean Journal of Clinical Pharmacy
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• v.31 no.2
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• pp.125-135
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• 2021

Background: Generally, pharmacokinetics (PK) models could be stratified into two models. The compartment PK model uses the concept of simple compartmentalization to describe complex bodies, and the physiologically based pharmacokinetic (PBPK) model describes the body using multi-compartment networking. Notwithstanding sharing a theoretical background in both models, there was still a lack of knowledge to enhance compatibility in both models. Objective: This study aimed to evaluate the compatibility among PBPK, lumping model and compartment PK model with voriconazole PK case study. Methods: The number of compartments and blood flow on each tissue in the PBPK model were modified using the lumping method, considering physiological similarities. The concentration-time profiles and area under the concentration-time curve (AUC) parameters were simulated at each model, assuming taken voriconazole oral 400 mg single dose. After that, those mentioned PK parameters were compared. Results: The PK profiles and parameters of voriconazole in the three models were similar that proves their compatibility. The AUC of central compartment in the PBPK and lumping model was within a 2-fold range compared to those in the 2- compartment model. The AUC of non-eliminating tissues compartment in the PBPK model was similar to those in the lumping model. Conclusion: Regarding the compatibility of the three PK models, the utilization of the lumping method was confirmed by suggesting its reliable PK parameters with PBPK and compartment PK models. Further case studies are recommended to confirm our findings.

• The Korea Journal of Herbology
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• v.22 no.1
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• pp.111-117
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• 2007

Objectives : The purpose of this study was to investigate the anti-inflammatory effects of extract from Pulsatilla koreana $N_{AKAI}$ (PK) on the peritoneal macrophage. Methods : To evaluate of anti-inflammatory of PK, we examined cytokines and NO production in lipopolysacchride (LPS)-induced macrophages. Furthermore, we examined molecular mechanism using western blot. Results : 1.Extract from PK reduced LPS-induced NO, tumor necrosis factor-a ($TNF-{\alpha}$), interleukin (IL)-6 and IL-12 production in peritoneal macrophages. 2.Extract from PK itself does not have any cytotoxic effect. PK inhibited the activation of extracelluar signal-regulated kinase(ERK 1/2) but not another mitogen-activated protein kinases (MAPKs) such as p38, c-Jun NH2-terminal kinase (JNK) and the degradation of inhibitory kappa B a ($I_{k}B_{a}$) does not any effect in the LPS-stimulated peritoneal macrophages. Conclusion : PK down-regulated LPS-induced NO and cytokines production, which may be provide a clinical basis for anti-inflammatory properties of PK.

• The Korea Journal of Herbology
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• v.25 no.2
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• pp.99-106
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• 2010

Objectives : This study was designed to investigate the effects of anti-oxidation of fractionated Pulsatilla koreana $N_{AKAI}$ (PK) extracts. And we examined to determine that a certain fractionated extract has the best anti-oxidative effects between the fractionated PK extracts. Methods : Anti-oxidative effects of fractionated PK extracts was measured by scavenging activities of DPPH, superoxide, nitric oxide (NO) and peroxynitrite radicals. And also scavenging activities of anti-oxidation in lipopolysaccharide (LPS)-treated RAW 264.7 cell was measured. After these examination, we determined a fraction that has best anti-oxidative effects. Results : Fractionated PK extracts inhibited radicals effectively. Also in RAW 264.7 cell, intracellular oxidation has inhibited by PK extracts. In these tests, ethyl acetate (EA) fraction has the best anti-oxidative effects among PK extracts. Conclusions : This results demonstrate that PK extracts exhibit anti-oxidative effects. And EA fraction has the best inhibition effects among the six fractions of PK.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.47 no.1
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• pp.23-30
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• 2021

This study is an experiment to evaluate the anti-atopy efficacy of five kinds of natural plant essential oils; Artemisia annua L. (AA), Citrus junos Sieb. ex TANAKA (CJ), Chrysanthemum boreale Makino (CB), Pinus koraiensis (PK), and Pinus densiflora for. erecta (PD). Through Agar diffusion test, five species of native plant essential oils were treated in a total of four strains, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. In order to invest the anti-inflammatory effect, five kinds of natural plant essential oils were treated in HaCaT cells-induced by TNF-α and IFN-γ (TI). AA, CJ, CB, PK and PD showed antibacterial effects on Candida albicans at a concentration of 10 mg/mL. We also found that the thymus and activation-regulated chemokine (TARC) expression was suppressed in 0.1 ㎍/mL of PK, 1 ㎍/mL of AA, CB, and PK. macrophage-derived chemokine (MDC) expression was suppressed in 1 ㎍/mL of AA and PK. IL-6 expression was suppressed in 0.1, 1 ㎍/mL of AA, PK in HaCaT cells. Hence it suggests that AA, CB, and PK have the anti-inflammatory effects, and it could contribute to atopic dermatitis relief by reducing the infiltration of immune cells to inflamed area.

• Korean Journal of Clinical Pharmacy
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• v.26 no.4
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• pp.312-317
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• 2016

Objective: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. Methods: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model ($NONMEM^{(R)}$ 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. Results: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. Conclusion: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.