• Biomolecules & Therapeutics
• /
• 제18권4호
• /
• pp.469-476
• /
• 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.

• 한국생물물리학회:학술대회논문집
• /
• 한국생물물리학회 1996년도 정기총회 및 학술발표회
• /
• pp.33-33
• /
• 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
• /
• 제19권3호
• /
• pp.364-370
• /
• 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
• /
• 제10권2호
• /
• pp.85-88
• /
• 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
• /
• 제22권1호
• /
• pp.68-72
• /
• 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
• /
• 제41권3호
• /
• pp.153-159
• /
• 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
• /
• 제19권4호
• /
• pp.498-503
• /
• 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
• /
• 제33권4호
• /
• pp.246-251
• /
• 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.

• 한국산학기술학회논문지
• /
• 제19권4호
• /
• pp.492-504
• /
• 2018

본 연구는 에스테틱과 메디컬에서 여드름 치료제로 잘 알려진 글리콜릭산필링과 해초필링, 일반스크럽제를 사용하여 모공각화증 피부에 미치는 영향을 살펴보고 모공각화증 피부 개선 프로그램의 기초 자료로 제시하고자 수행하였다. 실험방법은 실험군인 글리콜릭산필링(GP)군과 해초필링(SP)군, 대조군인 일반스크럽제(GS)군으로 분류하였으며, 모공각화증이 다소 많은 팔과 다리 부위를 각 군별 5부위씩 선정하여 6주간 시행하였다. 피부측정은 실험 전 0주차, 실험 2주차, 실험 4주차, 실험 6주차에 각질량, 유분량, 수분량, 색소침착을 측정하여 실험 전 후를 비교 분석하였다. 분석결과 실험군인 GP군은 실험 후 수분량 증가(t=-4.064, p<0.01)와 색소침착 감소(t=3.536, p<0.01), SP군은 실험 후 각질량의 감소(t=2.370, p<0.05)와 색소침착의 감소(t=4.017, p<0.01) 대조군인 GS군은 각질량의 감소(t=2.834, p<0.05)와 수분량의 증가(t=-7.589, p<0.001)로 유의미한 차이가 있는 것으로 나타났다. 또한 피부 자극 반응 차이에서는 GS군이 가장 자극일 적은 것으로 나타났다. 모공각화증 관리의 개선 만족도는 실험군의 SP군이 만족도가 가장 높은 것으로 나타났다. 동일한 제품으로 관리를 받은 의향에서는 실험군의 SP군과 GP군이 동일하게 높게 나타났으며, 실험군과 대조군 모두 모공각화증의 관리가 필요한 것으로 나타났다. 결론적으로 여드름의 치료제로도 많이 사용되는 해초필링, 글리콜릭산필링, 일반스크럽제는 모공 주변에 쌓인 각질을 제거하여 각질주기를 정상화시키고, 피부의 수분을 증가시켜 모공각화증 피부를 개선시키는 효과가 있음을 알 수 있었다. 따라서 모공각화증 피부 개선을 위해서는 적절한 각질제거와 피부장벽을 보호하는 보습제 사용이 꾸준히 함께 적용되어야 할 것이며, 향후 본 연구가 모공각화증 피부 개선 프로그램의 기초 자료로 사용이 가능할 것으로 사료된다.

• 한국식품영양과학회지
• /
• 제32권8호
• /
• pp.1262-1269
• /
• 2003

효소류의 떡 노화에 미치는 영향을 검토하였다. DSC 열특성의 검토에서 호화개시온도는 GP(glucoamylase+pullulanase)로 처리한 경우가 71.1$^{\circ}C$로 가장 낮고 그 다음이 $\beta$-amylase, $\alpha$-amylase 순이었다. 또 호화최대온도는 효소 처리한 것이 대조구에 비해서 대부분 낮은 편이었으며 그 중 GP처리한 것이 가장 낮은 것으로 나타났다. 또 떡의 용융 enthalpy는 GP, $\beta$-amylase, $\alpha$-amylase 순으로 증가하였으며 GP의 용융 enthalpy값이 다른 경우보다 많이 낮게 나타났다. 재결정도는 GP의 값이 크게 낮은 것으로 나타났다. Avrami exponent(n)는 0.90 ∼ 1.20 범위에 있었으며 노화속도의 시간상수 1/k은 GP, $\beta$-amylase, $\alpha$-amylase, Control의 순이었다. 효소류를 첨가한 떡의 조직감은 대조구에 비해서 차이를 보였으며 종류별 효과는 GP, $\beta$-, $\alpha$-amylase의 순으로 나타났다. L＊ 값은 $\beta$-amylase를 제외하고는 모두 감소하고 a＊ 값은 효소간 5% 수준에서 유의차를 나타내었다. b＊ 값의 경우는 GP는 청색 방향으로, $\beta$-, $\alpha$-amylase는 반대인 황색 방향으로 변하였다. 효소 처리한 떡의 관능검사는 효소 처리한 것이 대조구보다 다소 높은 값을 나타내어 좋은 관능성을 보여주었다.