• Journal of Microbiology and Biotechnology
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• v.34 no.6
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• pp.1229-1238
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• 2024

This study aimed to develop and assess a chitosan biomedical antibacterial gel ZincOxide-GrapheneOxide/Chitosan/β-Glycerophosphate (ZnO-GO/CS/β-GP) loaded with nano-zinc oxide (ZnO) and graphene oxide (GO), known for its potent antibacterial properties, biocompatibility, and sustained drug release. ZnO nanoparticles (ZnO-NPs) were modified and integrated with GO sheets to create 1% and 3% ZnO-GO/CS/β-GP thermo-sensitive hydrogels based on ZnO-GO to Chitosan (CS) mass ratio. Gelation time, pH, structural changes, and microscopic morphology were evaluated. The hydrogel's antibacterial efficacy against Porphyromonas gingivalis, biofilm biomass, and metabolic activity was examined alongside its impact (MC3T3-e1). The findings of this study revealed that both hydrogel formulations exhibited temperature sensitivity, maintaining a neutral pH. The ZnO-GO/CS/β-GP formulation effectively inhibited P. gingivalis bacterial activity and biofilm formation, with a 3% ZnO-GO/CS/β-GP antibacterial rate approaching 100%. MC3T3-e1 cells displayed good biocompatibility when cultured in the hydrogel extract.The ZnO-GO/CS/β-GP thermo-sensitive hydrogel demonstrates favorable physical and chemical properties, effectively preventing P. gingivalis biofilm formation. It exhibits promising biocompatibility, suggesting its potential as an adjuvant therapy for managing and preventing peri-implantitis, subject to further clinical investigations.

• Korean Journal of Clinical Pharmacy
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• v.22 no.1
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• pp.1-8
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• 2012

항혈소판제인 티크로피딘과 항고혈압제인 니칼디핀과의 약동학적 상호작용 연구를 위하여 티크로피딘 (3 또는 10 mg/kg)과 니칼디핀의 경구 (4 mg/kg) 및 정맥 (12 mg/kg) 투여하여 본 연구를 시행하였다. 연구방법: 티크로피딘이 cytochrome P450 (CYP) 3A4 활성과 P-glycoprotein (P-gp)의 활성에 미치는 영향도 평가하였다. 결 과: 티크로피딘과 니칼디핀의 병용투여 시 티크로피딘이 니칼디핀의 약물동태 파라미터에 미치는 결과는 다음과 같다. 티크로피딘은 CYP3A4 효소의 활성을 저해 하였으나 P-gp활성에는 영향을 미치지 못하였다. 니칼디핀의 혈중농도곡선하면적 (AUC)는 대조군에 비해 티크로피딘 10 mg/kg 병용투여군에서 유의성 (p < 0.05)있게 증가되었다. 상대적 생체이용률 (RB)은 티크로피딘 병용투여군에서 115-143%로 증가하였다. 결 론: 본 논문에서 흰쥐에 티크로피딘과 니칼디핀을 병용경구투여 시 니칼디핀의 생체이용률 (bioavailability)이 유의성 (p < 0.05)있게 증가된 것은 티크로피딘이 대사효소인 CYP3A4를 억제하여 소장과 간장에서 초회통과효과 (first-pass metabolism)를 감소 시켰기 때문인 것으로 사료된다. 본 실험결과를 토대로 인체에서 티크로피딘과 니칼디핀의 상호작용을 검토한 후 투여용량을 조절하는 것이 바람직하다고 사료된다.

• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.469-476
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• 2010

This study was to investigate the effect of apigenin on the bioavailability of paclitaxel after oral and intravenous administration in rats. The effect of apigenin on P-glycoprotein (P-gp), cytochrome P450 (CYP)3A4 activity was evaluated. The pharmacokinetic parameters of paclitaxel were determined in rats after oral (40 mg/kg) or intravenous (5 mg/kg) administration of paclitaxel with apigenin (0.4, 2 and 8 mg/kg) to rats. Apigenin inhibited CYP3A4 activity with 50% inhibition concentration ($IC_{50}$) of 1.8 ${\mu}M$. In addition, apigenin significantly inhibited P-gp activity. Compared to the control group, apigenin significantly increased the area under the plasma concentration-time curve (AUC, p<0.05 by 2 mg/kg, 59.0% higher; p<0.01 by 8 mg/kg, 87% higher) of oral paclitaxel. Apigenin also significantly (p<0.05 by 2 mg/kg, 37.2% higher; p<0.01 by 8 mg/kg, 59.3% higher) increased the peak plasma concentration ($C_{max}$) of oral paclitaxel. Apigenin significantly increased the terminal half-life ($t_{1/2}$, p<0.05 by 8 mg/kg, 34.5%) of oral paclitaxel. Consequently, the absolute bioavailability (A.B.) of paclitaxel was significantly (p<0.05 by 2 mg/kg, p<0.01 by 8 mg/kg) increased by apigenin compared to that in the control group, and the relative bioavailability (R.B.) of oral paclitaxel was increased by 1.14- to 1.87-fold. The pharmacokinetics of intravenous paclitaxel were not affected by the concurrent use of apigenin in contrast to the oral administration of paclitaxel. Accordingly, the enhanced oral bioavailability by apigenin may be mainly due to increased intestinal absorption caused via P-gp inhibition by apigenin rather than to reduced renal and hepatic elimination of paclitaxel. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced first-pass metabolism of paclitaxel via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by apigenin. It appears that the development of oral paclitaxel preparations as a combination therapy is possible, which will be more convenient than the i.v. dosage form.

• Proceedings of the Korean Biophysical Society Conference
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• 1996.07a
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• pp.33-33
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• 1996

An ectodomain of gp41, the transmembrane fusion protein of HIV, without the fusion peptide region was expressed using pET system in E. coli. The expressed protein gp41core, was isolated as inclusion body and was purified by ion-exchange chromatography after solubilized in 6M urea. The purified denatured protein was renaturated and the folded domain of gp41core was identified by the presence of the proteolysis resistence domain and a high content of ${\alpha}$-helical secondary structure. (omitted)

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.364-370
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• 2011

The purpose of this study was to investigate the effects of curcumin on the pharmacokinetics of loratadine in rats. The effect of curcumin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Pharmacokinetic parameters of loratadine were also determined after oral and intravenous administration in the presence or absence of curcumin. Curcumin inhibited CYP3A4 activity with an IC50 value of 2.71 ${\mu}M$ and the relative cellular uptake of rhodamine-123 was comparable. Compared to the oral control group, curcumin significantly increased the area under the plasma concentration-time curve and the peak plasma concentration by 39.4-66.7% and 34.2-61.5%. Curcumin also significantly increased the absolute bioavailability of loratadine by 40.0-66.1% compared to the oral control group. Consequently, the relative bioavailability of loratadine was increased by 1.39- to 1.67-fold. In contrast, curcumin had no effect on any pharmacokinetic parameters of loratadine given intravenously, implying that the enhanced oral bioavailability may be mainly due to increased intestinal absorption caused via P-gp and CYP3A4 inhibition by curcumin rather than to reduced renal and hepatic elimination of loratadine. Curcumin enhanced the oral bioavailability of loratadine in this study. The enhanced bioavailability of loratadine might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced fi rst-pass metabolism of loratadine via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by curcumin.

• Natural Product Sciences
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• v.10 no.2
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• pp.85-88
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• 2004

One hundred Indonesian plant extracts were screened to investigate their effects on the P-glycoprotein (P-gp) activity in human uterine sarcoma cells, MES-SA/DX5, for the first time. Among others, four samples, Alpinia galanga (BuOH ext.), Sindora sumatrana $(CHCl_3\;ext.)$, Strychnos ligustrina $(CHCl_3\;ext.)$, and Zingiber cassumunar Roxb (hexane ext.), exhibited the most potent inhibition on the P-gp activity. They increased cytotoxic activity of daunomycin up to $IC_{50}$ values of less than $1.41\;{\mu}M$, which is a value with a positive control, verapamil. Other 25 samples showed significant P-gp inhibitory activity with $IC_{50}$ values between 1.4 and $4.0\;{\mu}M$. These prospective samples will be subjected to further laboratory phytochemical investigation to find active principles.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.68-72
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• 2014

When chemotherapy is administered during pregnancy, it is important to consider the fetus chemotherapy exposure, because it may lead to fetal consequences. Paclitaxel has become widely used in the metastatic and adjuvant settings for woman with cancer including breast and ovarian cancer. Therefore, we attempted to clarify the transport mechanisms of paclitaxel through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of paclitaxel was time- and temperature-dependent. Paclitaxel was eliminated about 50% from the cells within 30 min. The uptake of paclitaxel was saturable with $K_m$ of $168{\mu}M$ and $371{\mu}M$ in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. [$^3H$]Paclitaxel uptake was markedly inhibited by cyclosporine and verapamil, well-known substrates of P-glycoprotein (P-gp) transporter. However, several MRP substrates and organic anions had no effect on [$^3H$]paclitaxel uptake in TR-TBT cells. These results suggest that P-gp may be involved in paclitaxel transport at the placenta. TR-TBT cells expressed mRNA of P-gp. These findings are important for therapy of breast and ovarian cancer of pregnant women, and should be useful data in elucidating teratogenicity of paclitaxel during pregnancy.

• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.153-159
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• 2011

This study was designed to investigate the effects of silibinin on the pharmacokinetics of carvedilol after oral administration of carvedilol in rats. Carvedilol was administered orally (3 mg/kg) with oral silibinin (0.3, 1.5 or 6 mg/kg) and intravenously (1 mg/kg) to rats. The effects of silibinin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 2C9 and CYP2D6 activity were also evaluated. Silibinin inhibited CYP2C9 and CYP2D6 enzyme activity with 50% inhibition concentration ($IC_{50}$) of 5.2 ${\mu}M$ and 85.4 ${\mu}M$, respectively. In addition, silibinin significantly enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. Compared with the control group, the area under the plasma concentration-time curve was significantly increased by 36.3-57.1%, and the peak concentration was significantly increased by 51.1-88.5% in the presence of silibinin after oral administration of carvedilol. Consequently, the relative bio-availability of carvedilol was increased by 1.13- to 1.57-fold and the absolute bioavailability was significantly increased by 38.6-59.7%. The time to reach peak concentration and the terminal half-life were not significant. The enhanced oral bio-availability of carvedilol may result from inhibition of CYP2C9-mediated metabolism and P-gp-mediated efflux of carvedilol rather than inhibition of CYP2D6-mediated metabolism in the intestine and/or in the liver by silibinin.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.498-503
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• 2011

The purpose of this study was to investigate the effects of nisoldipine on the pharmacokinetics of repaglinide in rats. The effect of nisoldipine on cytochrome P450 (CYP) 3A4 activity and P-glycoprotein (P-gp) were evaluated. The pharmacokinetic parameters of repaglinide were also determined in rats after oral (0.5 $mg{\cdot}kg^{-1}$) and intravenous (0.2 $mg{\cdot}kg^{-1}$) administration of repaglinide to rats without or with nisoldipine (0.3 and 1.0 $mg{\cdot}kg^{-1}$). Nisoldipine inhibited CYP3A4 enzyme activity with a 50% inhibition concentration of 5.5 ${\mu}M$. In addition, nisoldipine significantly enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. Compared to the oral control group, nisoldipine significantly increased the $AUC_{0-{\infty}}$ and the $C_{max}$ of repaglinide by 46.9% and 24.9%, respectively. Nisoldipine also increased the absolute bioavailability (A.B.) of repaglinide by 47.0% compared to the oral control group. Moreover, the relative bioavailability (R.B.) of repaglinide was 1.16- to 1.47-fold greater than that of the control group. Nisoldipine enhanced the oral bioavailability of repaglinide, which may be attributable to the inhibition of the CYP3A4-mediated metabolism in the small intestine and/or in the liver and to inhibition of P-gp in the small intestine rather than to reduction of renal elimination of repaglinide by nisoldipine. The increase in the oral bioavailability of repaglinide should be taken into consideration of potential drug interactions when co-administering repaglinide and nisoldipine.

• Acute and Critical Care
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• v.33 no.4
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• pp.246-251
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• 2018

Background: Target temperature management (TTM) improves neurological outcomes for comatose survivors of out-of-hospital cardiac arrest. We compared the efficacy and safety of a gel pad cooling device (GP) and a water blanket (WB) during TTM. Methods: We performed a retrospective analysis in a single hospital, wherein we measured the time to target temperature ($<34^{\circ}C$) after initiation of cooling to evaluate the effectiveness of the cooling method. The temperature farthest from $33^{\circ}C$ was selected every hour during maintenance. Generalized estimation equation analysis was used to compare the absolute temperature differences from $33^{\circ}C$ during the maintenance period. If the selected temperature was not between $32^{\circ}C$ and $34^{\circ}C$, the hour was considered a deviation from the target. We compared the deviation rates during hypothermia maintenance to evaluate the safety of the different methods. Results: A GP was used for 23 patients among of 53 patients, and a WB was used for the remaining. There was no difference in baseline temperature at the start of cooling between the two patient groups (GP, $35.7^{\circ}C$ vs. WB, $35.6^{\circ}C$; P=0.741). The time to target temperature (134.2 minutes vs. 233.4 minutes, P=0.056) was shorter in the GP patient group. Deviation from maintenance temperature (2.0% vs. 23.7%, P<0.001) occurred significantly more frequently in the WB group. The mean absolute temperature difference from $33^{\circ}C$ during the maintenance period was $0.19^{\circ}C$ (95% confidence interval [CI], $0.17^{\circ}C$ to $0.21^{\circ}C$) in the GP group and $0.76^{\circ}C$ (95% CI, $0.71^{\circ}C$ to $0.80^{\circ}C$) in the WB group. GP significantly decreased this difference by $0.59^{\circ}C$ (95% CI, $0.44^{\circ}C$ to $0.75^{\circ}C$; P<0.001). Conclusions: The GP was superior to the WB for strict temperature control during TTM.