• Journal of Pharmaceutical Investigation
• /
• 제34권6호
• /
• pp.505-511
• /
• 2004

A bioequivalence study of $Bestidine^{TM}$ tablets (Choong Wae Pharma. Corp., Korea) to Dong-A $Gaster^{TM}$ (Dong-A Pharmaceutical Co., Ltd., Korea) tablets was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the famotidine dose of 40 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of famotidine were monitored by a high-performance liquid chromatography for over a period of 12 hours after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the Cmax ratio for $Bestidine^{TM}/Gaster^{TM}$ were log 0.90-log 1.06 and log 0.98-log 1.20, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Bestidine^{TM}$ and $Gaster^{TM}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
• /
• 제38권2호
• /
• pp.135-142
• /
• 2008

The present study describes the evaluation of the bioequivalence of two atorvastatin tablets, Lipitor $Tablet^{(R)}$ (Pfizer, reference drug) and Atorva $Tablet^{(R)}$ (Yuhan, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Forty-nine healthy male Korean volunteers received each medicine at the atorvastatin dose of 40 mg in a $2{\times}2$ crossover study with a two weeks washout interval. After drug administration, serial blood samples were collected at a specific time interval from 0-48 hours. The plasma atorvastatin concentrations were monitored by an high performance liquid chromatography -tandem mass spectrometer (LC-MS/MS) employing electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.5 min and calibration curves were linear over the concentration range of 0.1-100 ng/mL for atorvastatin. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 48hr) was calculated by the linear log trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were complied trom the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Atorva $Tablet^{(R)}$ / Lipitor $Tablet^{(R)}$ were ${\log}\;0.9413{\sim}{\log}\;1.0179$ and ${\log}\;0.831{\sim}{\log}\;1.0569$, respectively. These values were within the acceptable bioequivalence intervals of ${\log}\;0.8{\sim}{\log}\;1.25$. Based on these statistical considerations, it was concluded that the test drug, Atorva $Tablet^{(R)}$ was bioequivalent to the reference drug, Lipitor $Tablet^{(R)}$.

• 폴리머
• /
• 제29권5호
• /
• pp.440-444
• /
• 2005

입자크기 감소에 의한 약물의 표면적 증가는 불용성 약물의 생체이용률 즉, 약물의 흡수량과 속도를 향상시켜 주는 효과적인 방법으로 알려져 있다. 그 동안 약물 나노제제 공정 동안 약물 나노입자가 응집되는 것을 방지하기 위한 안정제 또는 분산제로서 한정된 수의 부형제만 사용되어 공정의 개선에 제약이 되었다. 본 연구에서는 N-카복시안하이드라이드 단량체의 개환 중합으로 합성한 소수성과 친수성을 가진 아미노산 공중합체가 불용성 약물인 나프록센 나노입자를 안정화시키기 위한 새로운 물질로서 사용되었다. 합성된 아미노산 공중합체로 안정화된 나프록센 나노입자는 60분간 습식 분쇄 공정에 의해 $200\~500nm$의 크기로 제조되었고, 공중합체의 소수성 부분이 적어도 $10 mol\%$ 이상이어야 효과적인 크기 감소를 볼 수 있으며, 공중합체의 모폴로지와 분자량은 입자 크기 감소를 결정하는 중요 요소가 아니었다. 또한 제조된 약물 나노입자 크기는 눈에 띄는 응집없이 14일까지 안정한 것을 알 수 있었다.

• 약학회지
• /
• 제42권1호
• /
• pp.25-30
• /
• 1998

This study was designed to compare the absorption fraction and extent of ketoprofen gels and a matrix typed ketoprofen plaster patch. 3g (90mg as ketoprofen) of the two gels whi ch has oleohydrogel or hydrogel as a base, respectively, and 3 pieces of plaster patches (90mg as ketoprofen) were, applied in the area of 210$cm^2$ on forearm in 12 volunteers by cross over design. Blood samples were collected serially up to 24 hours and the plasma concentrations of ketoprofen were analyzed by HPLC using flurbiprofen as an internal standard. The detection limit of the assay was 1ng/ml of ketoprofen in plasma. The pharmacokinetic parameters (e.g. $AUC_{24hr}$, $AUMC_{24hr}$, MRT, Fraction Absorbed) were calculated from the plasma concentrations time data of each volunteer. The oleo-hydrogel showed significantly higher absorption fraction and extent of ketoprofen than the current hydrogel. The mean plasma concentrations of the oleo-hydrogel were increased to 98.46${\pm}$23.15ng/ml by 6 hour after application, and increased futher to 100.61${\pm}$18.65ng/ml at 24 hour. On the other hand, those of the hydrogel were increased 17.61${\pm}$18.65ng/ml at 5 hour to 34.68${\pm}$9.65ng/ml at 24 hour gradually. Therefore the plasma concentrations of oleo-hydrogel at each measured time were 3~7 times greater than those of the hydrogel with statistical significance. The $AUC_{24hr}$ (1797.26${\pm}$52.09ng.h/ml) of the oleo-hydrogel was 3.5 times greater (P<0.05) than that (516.17${\pm}$104.52ng.h/ml) of the hydrogel. The plaster patches showed higher bioavailability ($AUC_{24hr}$ 2877.37${\pm}$578.27ng.h/ml) than the olea-hydrogel ($AUC_{24hr}$ 1797.26${\pm}$52.09ng.h/ml) without statistical significance. But the absorption fraction of the oleo-hydrogel was rather higher than that of the plaster patches during the first 6 hours after administration. These results suggest that newly developed ketoprofen gel which is used oleo-hydrogel as a base would show excellent skin permeation on topical application for the corresponding clinical indications and could be absorbed as well as plaster patches.

• Parasites, Hosts and Diseases
• /
• 제61권3호
• /
• pp.282-291
• /
• 2023

Despite the recent progress in public health measures, malaria remains a troublesome disease that needs to be eradicated. It is essential to develop new antimalarial medications that are reliable and secure. This report evaluated the pharmacokinetics and antimalarial activity of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the rodent malaria parasite Plasmodium berghei in vivo. After a single oral dose (75 mg /kg) of N-89, its pharmacokinetic parameters were measured, and t_1/2 was 0.97 h, T_max was 0.75 h, and bioavailability was 7.01%. A plasma concentration of 8.1 ng/ml of N-89 was maintained for 8 h but could not be detected at 10 h. The dose inhibiting 50% of parasite growth (ED₅₀) and ED₉₀ values of oral N-89 obtained following a 4-day suppressive test were 20 and 40 mg/kg, respectively. Based on the plasma concentration of N-89, we evaluated the antimalarial activity and cure effects of oral N-89 at a dose of 75 mg/kg 3 times daily for 3 consecutive days in mice harboring more than 0.5% parasitemia. In all the N-89-treated groups, the parasites were eliminated on day 5 post-treatment, and all mice recovered without a parasite recurrence for 30 days. Additionally, administering oral N-89 at a low dose of 50 mg/kg was sufficient to cure mice from day 6 without parasite recurrence. This work was the first to investigate the pharmacokinetic characteristics and antimalarial activity of N-89 as an oral drug. In the future, the following steps should be focused on developing N-89 for malaria treatments; its administration schedule and metabolic pathways should be investigated.

• Journal of Ginseng Research
• /
• 제48권1호
• /
• pp.77-88
• /
• 2024

Background: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied. Methods: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model. Results: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation. Conclusion: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.