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To evaluate whether pu´er tea extracts and agar powder could be of benefit in the processing of Baekseolgi, 5 kinds of Baekseolgi were prepared using agar along with various concentrations (i.e., 1, 2, and 3%) of pu´er tea extracts. The pH and moisture contents were found to be 6.07-6.12 and 41.49-42.08% in the prepared PAB (Ⅰ), PAB (Ⅱ), and PAB (Ⅲ) Baekseolgi samples, respectively. In addition, a decrease in the L value and increases in the a and b values were found upon increasing the amount of pu´er tea extract employed. In terms of the texture evaluation, the control Baekseolgi sample (Con(Ⅱ)) supplemented with only agar showed a significantly lower cohesiveness and an increased hardness, while an increased cohesiveness and a reduced hardness were observed upon the addition of pu´er tea extracts. Furthermore, for the three Baekseolgi samples, the polyphenol contents ranged from 2.62 to 7.18 mg GAE/g, while DPPH radical scavenging activities of 21.27, 29.85, and 40.32% were recorded for PAB (Ⅰ), PAB (Ⅱ), and PAB (Ⅲ), respectively. In terms of the sensory evaluation, a higher level of pu´er tea extracts resulted in a poorer taste. More specifically, PAB (Ⅲ), supplemented with agar and 3% pu´er tea extracts, exhibited the lowest acceptability over the three samples. It was therefore considered that the addition of 1-2% pu´er tea extracts is optimal to improve the antioxidant properties of Baekseolgi without having a detrimental effect on the product quality.

This study was performed to evaluate the quality characteristics of Sikhyes (SBE-5, SBE-10, SBE-30, and SBE-50) prepared using various concentrations (5%, 10%, 30%, and 50%) of Sasa borealis extracts (SBE). There were no significant changes of pH and total acid contents in Sikhyes prepared with various concentration of SBE. Sikhye SBE-30 and Sikhye SBE-50 showed significantly higher contents in sweetness, reducing sugar, total polyphenol and flavonoid than other Sikhyes. In color, the more SBE was added, each Sikhye appeared the decreasing of L value, the increasing of b value and turbidity. In DPPH radical scavenging activity, there were no difference between Sikhye control (SBE free) and Sikhye SBE-5. But DPPH radical scavenging activity of Sikhye SBE-10, SBE-30 and SBE-50 increased proportionally as the concentration of SBE in Sikhyes were increased. The evaluation for taste tended to get high score in Sikhye SBE-30 and Sikhye SBE-50. The color preference decreased by additon of SBE. Overall preference showed a trend of decreasing in Sikhye SBE-50. These results indicates that the SBE could be beneficiary for preparation of Sikhye due to anti-oxidative effect, and the proper amounts of SBE would be about 30%.

PMK-S005 is synthetic s-allyl-l-cysteine (SAC), a sulfur-containing amino acid, which was initially isolated from garlic. The antioxidant and anti-inflammation activities of SAC have been demonstrated in diverse experimental animal models. The purpose of this study was to investigate the gastroprotective effects of PMK-S005 against NSAIDs-induced acute gastric damage in rats. Eight-week SD rats were pretreated with PMK-S005 (1, 5, or 10 mg/kg) or rebamipide (50 mg/kg) 1 h before administration of NSAIDs including aspirin (200 mg/kg), diclofenac (80 mg/kg), and indomethacin (40 mg/kg). After 4 h, the gross ulcer index, histological index, and gastric mucus level were determined. Myeloperoxidase (MPO), TNF-α, IL-1β, PGE2, and LTB4 levels were estimated in the gastric mucosal tissue by ELISA. Protein expressions of cPLA2, COX-1, and COX-2 were assessed by Western blot analysis. Pretreatment with PMK-S005 significantly attenuated the NSAIDs-induced gastric damage and increased the gastric mucus level. In addition, PMK-S005 attenuated increases in MPO, TNF-α, and IL-1β production. The expressions of cPLA2 and COX-2 induced by NSAIDs were decreased by PMK-S005 pretreatment. PMK-S005 did not cause suppression of PGE2 synthesis induced by NSAIDs, but LTB4 production was significantly suppressed by PMK-S005. The effects of PMK-S005 were consistently maximized at a concentration of 5 mg/kg, which were frequently superior to those of rebamipide. These results strongly suggest that PMK-S005 can be a useful gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, down-regulating cPLA2, COX-2 and LTB4 expression, and increasing the synthesis of mucus.

In Gyeongsangbuk-do seongju area, hundreds of tons of spoiled oriental melon are harvested annually. Therefore, ways to prevent such spoilage are needed. This study was conducted to investigate the quality characteristics of spoiled oriental melon juice after enzyme treatment for the production of oriental melon concentrate. The treatment of the oriental melon juice with three kinds of enzymes with variable concentrations showed the following results. PECE(1), which was compounded pectinase and cellulase at 0.01% (v/v), gave the melon a 0.16 brown color and 0.01 turbidity, and the highest L value of 97.00. The detected free sugar contents were fructose, glucose and sucrose, with the amount of sucrose the highest at roughly 4,000 mg%. The mixture of different enzyme treatments resulted in a 0.15 brown color and 0.01 turbidity at 60 minutes, and the L value was high at 97.25. The enzyme treatment temperatures of 50℃ and 60℃ yielded a low-level brown color and low turbidity, but the L values were high at 60℃ and 70℃. These results showed that 0.01% (v/v) mixing enzyme, i.e., pectinase and cellulose compounded at 60℃ for 60 min, must be used for the production of oriental melon concentrate.

계명대학교 식품가공학과This study was conducted to that investigate the quality characteristics of wet-ground whole-grain buckwheat powder for the buckwheat husk. The particle size of buckwheat rice was 74.84 μm, which was approximately four to five times larger than wet-ground whole buckwheat by wet grinding. The particle size showed that there was no significant difference after 90 min on wet grinding. The total phenolics and total flavonoids contents of the whole buckwheat powder were higher than those of buckwheat rice, and they gradually increased wet grinding progressed. The rutin contents of the buckwheat increased after wet grinding and was 152.90 ppm at 90 min. There was no significant difference in the quercetin contents after wet grinding at different times. The mineral contents (Ca, K and Mg) of the whole buckwheat powder were greater than those of the buckwheat rice. Further, Zn and Mn were detected in the whole buckwheat powder. The total amino acid content of the whole buckwheat powder increased to 22.27 mg%, and the important glutamic acid increased from 14.58 to 30.45 mg%. These study results were based on 90 min wet-grinding time for whole-buckwheat-powder manufacture. Whole buckwheat powder manufactured through wet grinding can be used as an active ingredient of buckwheat husk.Key words buckwheat, whole buckwheat powder, wet grinding, rutin

To stabilize the basal extraction conditions of Leonuri herbal products, three kinds of Leonurus sibiricus water extracts were prepared with different extraction conditions (boiling extraction (I), high thermal process & boiling extraction (II), and wet grinding & boiling extraction (III)), and their physiological properties were investigated. The extraction yields of the L. sibiricus water extracts were from 13.02 to 15.90%, with no significant difference among them. The polyphenol contents were significantly high in extracts (II) and (III) than in extract (I). The for the electron-donating ability was the smallest in extracts (II), (III) and (I) in ascending order. The ABTS radical scavenging ability was significantly higher in extracts (II) and (III) than in extract (I). Also, the ACE in hibition ability for 5 mg/mL of each extract was high in extracts (II) and (III), but there was no significant difference among the three extracts in terms of their nitrite scavenging abilities. Extraction processes (II) and (III) were shown to be useful for preparing Leonurus sibiricus water extracts with healthful properties.

Background/Aims This study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-l-cysteine (SAC; a sulfur-containing amino acid), against acute ethanol-induced gastric damage in rats.

A rapid, simple and fully validated LC-MS/MS method was developed and validated for the determination of megestrol acetate in human plasma using tolbutamide as an internal standard (IS) after one-step liquid–liquid extraction with methyl-tert-butyl-ether. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the transitions m/z 385.5 267.1 for megestrol acetate and m/z 271.4 155.1 for IS. Chromatographic separation was performed on a YMC Hydrosphere C18 column with an isocratic mobile phase, which consisted of 10 mm ammonium formate buffer (adjusted to pH 5.0 with formic acid)–methanol (60:40, v/v) at a flow rate of 0.4 mL/min. The achieved lower limit of quantitation (LLOQ) was 1 ng/mL (signal-to-noise ratio > 10) and the standard calibration curve for megestrol acetate was linear (r > 0.99) over the studied concentration range (1–2000 ng/mL). The proposed method was fully validated by determining its specificity, linearity, LLOQ, intra- and inter-day precision and accuracy, recovery, matrix effect and stability. The validated LC-MS/MS method was successfully applied for the evaluation of pharmacokinetic parameters of megestrol acetate after oral administration of a single dose 800 mg of megestrol acetate (Megace™) to five healthy Korean male volunteers under fed conditions. Copyright © 2012 John Wiley & Sons, Ltd.

Sulfuretin, a flavonoid isolated from heartwood of Rhus verniciflua, has been reported to have anti-cancer activities but the underlying molecular mechanism was not clear. In this study, sulfuretin induced apoptosis by activating caspases-8, -9, and -3 as well as cleavage of poly(ADP-ribose) polymerase. Furthermore, treatment with sulfuretin caused mitochondrial dysfunctions, including the loss of mitochondrial membrane potential (ΔΨ(m)), the release of cytochrome c to the cytosol, and the translocations of Bax and tBid. Sulfuretin also activated the extrinsic apoptosis pathway, that is, it increased the expressions of Fas and FasL, the activation of caspase-8, and the cleavage of Bid. Furthermore, blocking the FasL-Fas interaction with NOK-1 monoclonal antibody prevented the sulfuretin-induced apoptosis. The therapeutical effect of sulfuretin in leukemia is due to its potent apoptotic activity through the extrinsic pathway driven by a Fas-mediated caspase-8-dependent pathway.

Ethnopharmacological relevance IH-901 (20-O-beta- d -glucopyranosyl-20(S)-protopanaxadiol) is a novel ginseng saponin metabolite formed by human intestinal bacteria and is known to have antitumor and antimetastatic effects. However, there has been no pharmacokinetic study of IH-901 in human beings. Aim of the study The aim of this study was to investigate the pharmacokinetic differences of IH-901 from fermented and non-fermented ginseng. Materials and methods To investigate whether the pharmacokinetics of IH-901 differ between fermented and non-fermented ginseng, an open label, randomized, single dose, fasting, two-period, cross-over, pharmacokinetic study was conducted. A total of 24 healthy Korean male volunteers participated in this study. All subjects were allocated into two equal groups and administered 3 g of fermented or non-fermented Panax ginseng. Serial blood samples for pharmacokinetic analysis were collected in the 24 h after dosing. Plasma IH-901 concentration was measured by a validated high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. Pharmacokinetic parameters including AUCt, Cmax, and Tmax were calculated by noncompartmental models in the BA-CALC program (KFDA, 2008, 1.0.0, Korea). Results After oral administration of fermented ginseng, 5 subjects experienced diarrhea. The means of AUCt and Cmax were significantly different between the two groups. In the fermented ginseng group, AUCt was 2083.09 ± 91.97 ng h/mL, a 15.5-fold increase over that of IH-901 from the non-fermented group (134.50 ± 63.10 ng h/mL), and the mean Cmax was 325.00 ± 91.97 ng/mL in the fermented ginseng group, a 27-fold higher value than that in the non-fermented group (13.88 ± 7.24 ng/mL). Tmax was 3.29 ± 1.00 and 12.04 ± 4.96 h in the fermented and non-fermented group, respectively. Conclusions The results of this study showed that the pharmacokinetic parameters of IH-901 from fermented Panax ginseng are different from those of non-fermented ginseng, from which IH-901 is formed by intestinal fermentation.

A sensitive and specific liquid chromatographic method coupled with tandem mass spectrometry (LC-MS/ MS) was developed for the analysis of ambroxol (active moiety of acebrophylline). After acetonitrile precipitation of proteins from plasma samples, ambroxol and the domperidone (internal standard, IS) were eluted on a C18 column. The isocratic mobile phase was consisted of 10 mM ammonium acetate and methanol (10 : 90, v/v), with flow rate at 0.2 mL/min. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z 379.2→264.0 and the m/z 426.2→175.1 transitions for ambroxol and the IS, respectively. Twenty four healthy Korean male subjects received two capsules (100 mg × 2) of either the test or the reference formulation of acebrophylline HCl in a 2 × 2 crossover study, this was followed by a 1week washout period between either formulation. AUC0-t (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. Cmax (maximum plasma drug concentration) and Tmax (time to reach Cmax) were compiled from the plasma concentration-time data. The 90% confidence intervals for the log transformed data were acceptable range of log 0.8 to log 1.25 (e.g., log 0.8964 - log 0.9910 for AUC0-t log 0.8690 - log 1.0750 for Cmax). The major parameters, AUC0-t and Cmax met the criteria of Korea Food and Drug Administration for bioequivalence indicating that Acephyll(R) capsule (test) is bioequivalent to Surfolase(R) capsule (reference).

− A rapid and specific high performance liquid chromatography-tandem mass (LC/MS/MS) method for theanalysis of montelukast in human plasma has been developed and validated. After cold acetonitrile-induced precipitation ofthe plasma samples, montelukast and glipizide (internal standard, IS) were eluted on a reverse-phase C 18 column by isocraticmobile phase consisted of 10 mM ammonium formate buffer (adjusted to pH 3.5 with formic acid) and acetonitrile (3:97,v/v). Acquisition was performed with multiple reaction monitoring (MRM) mode by monitoring the transitions: m/z 587.2 → 423.2 for montelukast and m/z 446.0 → 321.2 for IS. Ranges of concentration for calibration curves (10-1000 ng/mL) showedcorrelation coefficients (r 2 ) were better than 0.9948. Precision of intra- and inter-day ranged from 3.70 to 11.68% and from3.04 to 12.95%, accuracy of intra-day and inter-day ranged from 93.34 to 102.75% and from 100.79 to 107.63%, respec-tively. The described method provides a fast and sensitive analytical tool for determining montelukast levels in plasma, andwas successfully applied to a pharmacokinetic study in 16 healthy human subjects after oral administration of 10mg tabletformulation of montelukast sodium under fasting conditions.Key words

Method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of pregabalin in plasma samples. Acquisition was performed by monitoring the tran- sitions: m/z 160.1→142.2 for pregabalin and m/z 423.2→207.1 for losartan (as an internal standard). After cold acetonitrile- induced protein precipitation of the plasma samples, separation was performed with C18 column by isocratic mobile phase consisted of 10 mM ammonium acetate and acetonitrile (15:85, v/v). Results were linear over the concentration ranged from 0.1 to 10 µg/mL and the correlation coefficients (r) were ≥0.99. Intra- and inter-day precisions were ≤6.02 and ≤11.04%, respectively, and intra- and inter-day accuracies were 96.60-101.09 and 98.10-102.60%, respectively. This validated method was successfully applied to a bioequivalence study of two formulations of pregabalin, Daewoong pregabalin capsule (Dae- woong Pharm. Co., Ltd.) and Lyrica ® capsule (Pfizer Korea Ltd.) in twenty eight healthy Korean volunteers. The subjects received a single oral dose of each formulation (150 mg as pregabalin) in a randomized 2 × 2 crossover study and plasma samples were obtained from each subject at predetermined time intervals. Then, the pharmacokinetic parameters (AUC0-t, Cmax and Tmax) were calculated and statistically analyzed to assess the differences between two formulations. The 90% con- fidence intervals for the log-transformed data were acceptable range of log 0.8-log 1.25 (e.g., log 1.0048-log 1.0692 for AUC0-t, log 0.9142-log 1.0421 for Cmax). Thus, AUC0-t and Cmax met the criteria of the Korea Food and Drug Administration (KFDA) for bioequivalence test indicating that Daewoong pregabalin capsule was bioequivalent to Lyrica ® capsule.

In the previous article we have reported that 3,4-dihydroquinazoline 1 is a potent and selective T-type calcium channel blocker that exhibited strong anti-cancer activity in vitro. Compound 1·2HCl was further in vivo evaluated against A549 xenograft in BALB/c nude mice, which exhibited 49% tumor-weight inhibition through intravenous administration of 2 mg/kg of body weight and was more potent than doxorubicin. Moreover, compound 1·2HCl has an oral bioavailability of 98% with LD(50) values of 693 mg/kg (p.o. route) and 40.0 mg/kg (i.v. route) of body weight. In addition, its efficient scale-up synthetic method was developed.

We describe a simple, rapid and sensitive high-performance liquid chromatography–electrospray ionization tandem mass spectrometric method that was developed for the simultaneous determination of carebastine and pseudoephedrine in human plasma using cisapride as an internal standard. Acquisition was performed in multiple-reaction monitoring mode by monitoring the transitions: m/z 500.43 > 167.09 for carebastine and m/z 166.04 > 147.88 for pseudoephedrine. The devised method involves a simple single-step liquid–liquid extraction with ethyl acetate. Chromatographic separation was performed on a C18 reversed-phase chromatographic column at 0.2 mL/min by isocratic elution with 10 mM ammonium formate buffer–acetonitrile (30:70, v/v; adjusted to pH 3.3 with formic acid). The devised method was validated over 0.5–100 ng/mL of carebastine and 5–1000 ng/mL of pseudoephedrine with acceptable accuracy and precision, and was successfully applied to a bioequivalence study involving a single oral dose (10 mg of ebastine plus 120 mg of pseudoephedrine complex) to healthy Korean volunteers. Copyright © 2010 John Wiley & Sons, Ltd.

This study investigated the effects of water-soluble calcium supplements manufactured with eggshells and oyster shells on growing rats. The aim was to review the potential use of food wastes as materials for water-soluble calcium supplements as compared to water-soluble calcium supplements made from imported seaweed powder. When experimental animals were administered three types of water-soluble calcium supplements orally for six weeks, the serum calcium level of the seaweed calcium supplement group were significantly higher than that of eggshell or oyster shell-derived calcium, but blood alkali phosphatase activity, osteocalcin and urine crosslink levels were not different in the three types of calcium supplements. Bone mineral density and bone mineral content in spine, femur and tibia also were not significantly different among the groups. However, when considering body weight of each group, bone mineral density and bone mineral content of the femur were significantly higher in the oyster shell calcium supplement group. These results suggest that at least on a short-term basis, the effect of calcium supplements prepared from eggshell and oyster shell are similar to the effects of seaweed calcium supplements.

The purpose of the present study was to evaluate the bioequivalence of meloxicam capsule, capsule( Boehringer Ingelheim Ltd., Korea) as a reference drug and capsule (Kukje Pharma Ind. Co., Ltd., Korea) as a test drug, according to the guidelines of Korea Food and Drug Administration(KFDA). Thirty two healthy male Korean volunteers received capsule containing meloxicam 7.5 mg in a crossover study. There was a one-week above washout period between the doses. Plasma concentrations of meloxicam were monitored for over a period of 72 hr after administration by using a high performance liquid chromatography-tandem mass spectrometer(LC-MS/MS). (the area under the plasma concentration-time curve from time zero to 72 hr), (maximum plasma drug concentration) and (time to reach ) were complied from the plasma concentration-time data. Analysis of variance(ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed and . The 90% confidence intervals of the ratio and the ratio for were log 0.8605-log 0.9847 and log 0.9765-log 1.1503, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25, recommended by KFDA. In all of these results, we concluded that capsule was bioequivalent to capsule, based on the rate and extent of absorption.

A rapid and simple procedure was developed for the determination of cephradine in human plasma using liquid chromatography coupled with electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). After trichloroacetic acid (TCA) precipitation of proteins from plasma samples, cephradine and cefaclor (the internal standard; IS) were eluted on a CN column. The isocratic mobile phase used consisted of acetonitrile-water-formic acid (25:75:0.1, v/v/v). Cephradine and the IS were both detected in multiple reaction monitoring (MRM) mode at the transitions: m/z 350.0 --> 90.8 for cephradine and m/z 368.1 --> 106.0 for the IS, respectively. The calibration curve was linear over the concentration range from 0.05 to 50 microg/ml, and correlation coefficients were greater than 0.996. The coefficient of variation of assay precision was less than 9.36%, and its accuracy ranged from 87.92% to 111.16%. The chromatographic run time for each plasma sample was less than 3 min. The developed method was successfully applied to a bioequivalence study of cephradine in healthy male volunteers.

The purpose of this study was to evaluate the bioequivalence of two nateglinide tablets, tablet (ILDONG Pharm. Co., Ltd., Seoul, Korea, reference drug) and tablet (ILHWA. Co., Ltd., Seoul, Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Thirty-five healthy male volunteers, years in age and in body weight, were divided into two groups and a randomized cross-over study was employed. After a tablet containing 90 mg of nateglinide was orally administrated, blood was taken at predetermined time intervals over a period of 8 hr and concentrations of nateglinide in plasma were monitored using LC-MS/MS. Pharmacokinetic parameters such as AUCt (the area under the plasma concentration-time curve from time 0 to 8 hr), (maximum plasma drug concentration) and (time to reach ) were calculated and analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed and and untransformed . The 90% confidence intervals of the ratio and the ratio for were and , respectively. Since these values were within the acceptable bioequivalence intervals of , recommended by KFDA, it was concluded that tablet was bioequivalent to tablet, in terms of both rate and extent of absorption.

The purpose of the present study was to evaluate the bioequivalence of two pioglitazone HCl tablets, , tablets (Lilly Korea. Ltd., Korea) as a reference drug and , tablets (Reyon Pharm. Co., Ltd., Korea) as test drug, according to the guideline of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received one tablet containing pioglitazone HCl 15 mg in a crossover study. There was a one-week washout period between the doses. Plasma concentrations of pioglitazone were monitored for over a period of 36 hr after administration by using a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under the plasma concentration-time curve from time zero to 36 hr (), maximum plasma drug concentration () and time to reach () were complied from the plasma concentration-time data. Analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed and . The 90% confidence intervals of the ratio and the ratio for /. were log 0.8753-log 1.1286 and log 0.8669-log 1.1734, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25, recommended by KFDA. In all of these results, we concluded that the . tablet was bioequivalent to the . tablet, based on the rate and extent of absorption.

A simple LC-MS/MS method of rabeprazole in human plasma was developed and validated. Rabeprazole and Internal standard (I.S), omeprazole, were extracted from human plasma by liquid liquid extraction, chromatographic separation of rabaprazole in plasma was achieved at with a Shiseido UG120 column and methanol-10 mM ammonium acetate buffer (pH 9.42 with ammonium water), as mobile phase. Rabeprazole produced a protonated precursor ion [] at m/z 360.10 and corresponding product ion at m/z 242.21. Internal standard produced a protonated precursor ion [] at 346.09 and corresponding product ion at m/z 198.09. This method showed linear response over the concentration range of with correalation coefficient greater than 0.99. The lower limit of quantitation (LLOQ) using 0.2 mL plasma was 1 ng/mL, which was sensitive enough for pharmacokinetics studies. The method was specific and validated with a limit of quantitation of 1 ng/mL. The intra-day and inter-day precision and accuracy were acceptable for all samples including the LLOQ. The applicability of the method was demonstrated by analysis of plasma after administration of a single 10 mg dose to 36 healthy subject. From the plasma rabeprazole concentration versus time curves, the mean (The area under the plasma concentration-time curve from time 0 to 12 hr ) was , (maximum plasma drug concentration) of reached after adiministration. The mean biological half-life of rabeprazole was . Based on the results, this simple method could readily be used in pharmacokinetics studies.

The aim of the present study was to evaluate the bioequivalence of two domperidone maleate tablets, Motilium- Tablet (Janssen Korea Ltd., reference product) and Tablet (Daewon Pharm. Co., Ltd., test product). Domperidone was extracted by liquid-liquid extraction using tert-butyl methyl ether and separated in less than 3 min on reverse-phase column using an isocratic elution. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z and the m/z transitions for domperidone and the internal standard (roxithromycin), respectively. Calibration curves, from ng/mL of domperidone, showed correlation coefficients (r) higher than 0.9941. Intra day and inter day precision (C.V. %) for quality control were ranged from 10.04 to 16.09% and from 10.87 to 18.69%, respectively. The lower limit of quantification (LLOQ) of domperidone was 0.05 ng/mL. The method described is precise and sensitive and has been successfully applied to the study of bioequivalence of domperidone in 24 healthy Korean volunteers. Twenty-four healthy male Korean volunteers received a single dose of each medicine ( domperidone maleate) in a crossover study. There was a one-week washout period between the doses. Plasma concentrations of domperidone were monitored for over a period of 24 hr after the administration. (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. (maximum plasma drug concentration) and (time to reach ) were compiled from the plasma concentration-time data. The 90% confidence intervals for the log transformed data were within acceptable range of log 0.8 to log 1.25 (e.g., for , for ). The major parameters, and met the criteria of KFDA for bioequivalence indicating that tablet is bioequivalent to Motilium- tablet.

The purpose of the present study was to evaluate the bioequivalence of two etodolac capsules, Kuhnillodin capsule (Kuhnil. Co., Ltd., Seoul, Korea) as reference drug and Etodin capsule (Myungmun Pharm. Co., Ltd., Seoul, Korea) as test drug, according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-three healthy male Korean volunteers received one capsule at the dose of 200 mg etodolac in a crossover study. There was a one-week washout period between the doses. Plasma concentrations of etodolac were monitored by a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) for over a period of 24 hr after the administration. was calculated by the linear trapezoidal rule method. and were compiled from the plasma concentration-time data. Analysis of variance (ANOVA) was carried out using logarithmically transformed and . The 90% confidence intervals of the ratio and the ratio for Etodin/Kuhnillodin were and , respectively. These values were within the acceptable bioequivalence intervals of . Thus, our study demonstrated that Etodin was bioeqiovalent to Kuhnillodin preparation when the rate and extent of absorption between two preparations were compared.

The purpose of the present study was to evaluate the bioequivalence of two levofloxacin tablets, Jeil tablet (Jeil Pharm. Co., Ltd., Korea, reference drug) and tablet (Ilhwa. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received two tablets containing levofloxacin 200 mg in a crossover study. There was a one-week washout period between the doses. Plasma concentrations of levofloxacin were monitored for over a period of 24 hr after administration by using a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under the plasma concentration-time curve from time zero to 24 hr (), maximum plasma drug concentration () and time to reach were complied from the plasma concentration-time data. Analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed and . The 90% confidence intervals of the ratio and the ratio for /Jeil were and , respectively. These values were within the acceptable bioequivalence intervals of , recommended by KFDA. In all of these results, we concluded that tablet was bioequivalent to Jeil tablet, in terms of rate and extent of absorption.

The purpose of the present study was to evaluate the bioequivalence of two topiramate tablets, Topamax tablet (Janssen Korea. Co., Ltd., Seoul, Korea, reference drug) and Topamin tablet (Myungmoon Pharm. Co., Ltd., Seoul, Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received one tablet at the dose of 100 mg topiramate in a crossover study. There were two-weeks washout period between the doses. Plasma concentrations of topiramate were monitored by an LC-MS/MS for over a period of 96 hr after administration. (the area under the plasma concentration-time curve from time zero to 96 hr) was calculated by the linear trapezoidal rule method. (maximum plasma drug concentration) and (time to reach ) were compiled from the plasma concentration-time data. Analysis of variance (ANOVA) was carried out using logarithmically transformed and . The 90% confidence intervals of the , ratio and the ratio for Topamin/Topamax were and , respectively. These values were within the acceptable bioequivalence intervals of . Taken together, our study demonstrated the bioequivalence of Topamax and Topamin with respect to the rate and extent of absorption.

Within the elderly population, the use of calcium supplements and the intake of calcium from food are on the rise in order to maintain health. Calcium is absorbed as an ion in vivo, leading to speculation that absorption efficiency is affected by the solubility of the calcium consumed. In our study, the bioavailability of two types of calcium supplements with different solubilities was evaluated. Experimental animals were fed water-soluble or insoluble calcium supplements for 6 weeks. We found that blood alkali phosphatase activity, osteocalcin content, and urine crosslinks values were not different between the groups. Similarly, the degree of apparent calcium absorption between the two calcium supplements was not significantly different. The bone mineral density and bone mineral content of the femur and the tibia increased in the group that consumed insoluble calcium compared with those of the water-soluble calcium supplemented group. However, when considering body weight, the bone mineral density value for all areas, including the spine, was significantly higher in the group that consumed the water-soluble calcium supplement.

The purpose of the present study was to evaluate the bioequivalence of two baclofen tablets, tablet (Yooyoung Pharm. Co., Ltd., Seoul, Korea, reference drug) and Taepyungyang Baclofen tablet (Pacificpharma Corporation, Seoul, Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received three tablets containing baclofen 10 mg in a crossover study. There was a one-week washout period between the doses. Plasma concentrations of baclofen were monitored for over a period of 24 hr after the administration by using an LC-MS/MS. were compiled from the plasma concentration-time data. Analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed . The 90% confidence intervals of the and the for Taepyungyang were , respectively. These values were within the acceptable bioequivalence intervals of . It was concluded that Taepyungyang Baclofen tablet was bioequivalent to tablet, in terms of both rate and extent of absorption.

We developed and validated a simple high-performance liquid chromatography (HPLC) coupled with positive ion electrospray ionization tandem mass spectrometry (ESI-MS/MS) detection system for determining penciclovir (active metabolite of famciclovir) levels in human plasma using acyclovir as an internal standard (IS). Acquisition was performed in multiple reaction monitoring (MRM) mode by monitoring the transitions: m/z 254.00>152.09 for penciclovir and m/z 226.00>152.09 for IS. The analytes were chromatographed on a Capcellpak MGII C(18) reversed-phase chromatographic column by isocratic elution using 30% methanol and 70% Milli-Q water containing 10 mM ammonium formate (adjusted to pH 3.1 with formic acid). Results were linear over the studied range (0.05-10 microg/ml) with r(2)=0.9999, and the total analysis time for each run was 2 min. Intra- and inter-assay precisions were 2.3-7.8 and 3.7-7.5%, respectively, and intra- and inter-assay relative errors (RE) were 2.0-8.4 and 1.9-9.1%, respectively. The lower limit of quantification (LLOQ) was 0.05 microg/ml. At this concentration mean intra- and inter-assay precisions were 7.8 and 7.5%, respectively, and mean intra- and inter-assay relative errors were 2.2 and 9.1%, respectively. Penciclovir was found to be stable in plasma samples under short-, long-term storage and processing conditions. The developed assay was successfully applied to a bioequivalence study of penciclovir administered as a single oral dose (500 mg as famciclovir) to healthy volunteers.

The purpose of the present study was to evaluate the bioequivalence of two donepezil tablets, tablet (Dae Woong Pharm. Co., Ltd., Korea, reference drug) and tablet (Dong Wha Pharm. Ind. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received one tablet containing donepezil hydorchloride 10 mg in a crossover study. There was a three-week washout period between the doses. Plasma concentrations of donepezil were monitored by an LC-MS/MS far over a period of 240 hr after the administration. , (the area under the plasma concentration-time curve from time zero to 240 hr) was calculated by the linear trapezoidal rule method. (maximum plasma drug concentration) and (time to reach )were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed and , No significant sequence effects were found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the and were log 0.95log 1.03 and log 0.94log 1.08, respectively. These values were within the acceptable bioequivalence intervals of log 0.80log 1.25. Taken together, our study demonstrated the bioequivalence of and with respect to the rate and extent of absorption.

In this study, the main purpose was to evaluate the bioequivalence of two thioctic acid tablests, Thioctacid HR tablet(Bukwang Pharm. Co., Ltd.) and Daewon thioctic acid HR tablet 600 mg(Daewon Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration(KFDA). Twenty-four, healthy Korean volunteers were divided into two groups, randomized and treated by crossover study. After the administration of one thioctic acid tablet containing 600 mg thioctic acid, blood samples were taken until 8 hr after the oral administration. LC-MS/MS was applied to determination of thioctic acid, and we calculated the from the plasma concentration-time data. Analysis of variance(ANOVA) was carried out using logarithmically transformed . 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 ratio and the ratio for Daewon thioctic acid tablet 600 mg/Thioctacid HR were log 0.9877log 1.1938 and log 0.8169log 1.2237, respectively. These values were within the acceptable bioequivalence intervals of log 0.80log 1.25, recommended by KFDA. In all of these results we concluded that Daewon thioctic acid tablet 600 mg was bioequivalent to Thioctacid HR tablet, in terms of rate and extent of absorption.

The purpose of the present study was to evaluate the bioequivalence of two zolpidem tartrate tablets, Stilnox tablet(Sanofi-aventis Korea, reference product) and Zanilo tablet(ChoDang Pharm Co., Ltd., Korea, test product), according to the guidelines of Korea Food and Drug Administration(KFDA). After adding an internal standard(cimetropium), 250 plasma samples were extracted using 1.3 mL of ethyl acetate. Extracted compounds were analyzed by HPLC with triple-quadrupole mass spectrometry. This method for determination of zolpidem is proved accurate and reproducible with the limit of quantitation of 1 ng/mL in human plasma. Twenty-four healthy male Korean volunteers received each medicine at the zolpidem tartrate dose of 10 mg in a crossover study. There was one-week washout period between the doses. Plasma concentrations of zolpidem were monitored for over a period of 8 hr after the administration. (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. (maximum plasma drug concentration) and (time to reach ) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed and . No significant sequence effect was found for all of the bio-availability parameters indicating that the crossover design was properly performed. The 90% confidence intervals for the log transformed data were acceptable range of log 0.8 to log 1.25(e.g., log 0.92-log 1.06 for , log 0.96-log 1.13 for ). The major parameters, and met the criteria of KFDA for bioequivalence indicating that Zanilo tablet is bioequivalent to Stilnox tablet.

The purpose of the present study was to evaluate the bioequivalence of two losartan tablets, tablet (MSD Korea. Co., Ltd., Seoul, Korea, reference drug) and tablet (DaeWon Pharm. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received two tablets at the losartan kalium dose of 100 mg in a crossover study. There was a one-week washout period between the doses. Plasma concentrations of losartan were monitored by an LC-MS/MS for over a period of 12 hr after the administration. (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. (maximum plasma drug concentration) and (time to reach ) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed and . 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 ratio and the ratio for were , respectively. These values were within the acceptable bioequivalence intervals of . Taken together, our study demonstrated the bioequivalence of and with respect to the rate and extent of absorption.

The purpose of this study was to evaluate the bioequivalence of two amlodipine maleate tablets, SKAD tablet (SK Pharma. Co., Ltd., Seoul, Korea, reference drug) and A-PINE tablet (Daewon Pharm. Co., Ltd., Seoul, Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male volunteers, years in age and kg in body weight, were divided into two groups and a randomized crossover study was employed. After a tablet containing 6.42 mg of amlodipine maleate was orally administrated, blood was taken at predetermined time intervals over a period of 144 hr and concentrations of amlodipine in plasma were monitored using LC-MS/MS. Pharmacokinetic parameters such as (the area under the plasma concentration-time curve from time zero to 144 hr), (maximum plasma drug concentration) and (time to reach ) were calculated and analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed and , and untransformed . 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 ratio and the ratio for A-PINE/SKAD were and , respectively. Since these values were within the acceptable bioequivalence intervals of , recommended by KFDA, it was concluded that A-PINE tablet was bioequivalent to SKAD tablet, in terms of both rate and extent of absorption.

In the present study, we developed a method coupling liquid-liquid extraction (LLE) to high-performance liquid chromatography (HPLC) with positive ion electrospray ionization tandem mass spectrometry (ESI-MS/MS) to determine zaltoprofen levels in human plasma, using enalapril as internal standard (IS). The high sensitivity and specificity of MS/MS detection enabled the use of small plasma volumes (250 microL) and a simple LLE procedure. Furthermore, the short run-times (2 min) involved are compatible with the requirements of large-scale clinical studies. Ion acquisition was performed in multiple reaction monitoring (MRM) mode by monitoring the transitions m/z 299.3 > 225.0 for zaltoprofen and m/z 377.4 > 234.2 for the IS enalapril. The limit of detection (LOD) was 0.01 microg/mL and the lower limit of quantitation (LLOQ) was 0.05 microg/mL. The devised method was linear over the studied range (0.05-20 microg/mL), with r2 > 0.99 and a run-time of 2 min. Intra-day precisions fell in the range 2.0-13.8%, inter-day precisions in the range 2.1-3.9%, and intra- and inter-day accuracies in the range 102.8-114.1%. The described method provides a fast and sensitive analytical tool for zaltoprofen and was successfully applied to a 24-subject pharmacokinetic study.

체중조절을 희망하는 여대생 18명을 대상으로, 자의적 행동수정을 위한 상담프로그램과, 개별ㆍ그룹별 운동프로그램으로 구성된 복합식 체중조절 프로그램에 참여하도록 하여 활용도에 대해 조사하였다. 대상자는 대구ㆍ경북 지역에 거주하는 평균 연령 21.3세, 평균 신장 161.8 cm의 여대생이었으며, 체질량지수(BMI)에 따라 과체중군(25≤BMI＜27)과 비만군(BMI≥27)으로 구분하였다. 대상자들의 초기 평균 체중과 체질량지수는 각각 71.56 ㎏, 27.25 ㎏/㎡였으며, 프로그램 참여 동기는 대다수가 외모에 대한 자신감 결여 때문이었다. 9주간의 체중조절 프로그램으로 과체중군은 3.28 ㎏, 비만군은 3.0 ㎏의 체중감소가 있었으며, 체지방은 과체중군에서 1.61%, 비만군에서 0.8% 감소하였다. 총콜레스테롤과 LDL-콜레스테롤은 과체중군에서 유의적(p＜0.05)으로 감소하였으며, 최대산소섭취량 또한 체중조절 프로그램 종료후 과체중군에서 2.71 mL/㎏/min 증가하였다. 비만군은 체중조절 과정을 통해 열량섭취량이 권장량 대비 109.2%에서 86.5%로 감소하였으며, 식사속도, 간식섭취 및 식사중 TV시청 빈도의 식행동 평가점수가 높아졌다. 본 자율적 체중조절프로그램은 과체중군의 체중감량에 효과가 있을 것으로 추측되나 비만군은 자율적 운동에 소극적인 성향을 나타내고 있어, 비만정도에 따라 체중조절 프로그램의 구성과 진행을 달리할 필요성이 있겠다.

We evaluated the possibility of rapid fermentation of anchovy sauce using a commercial protease. The fermentation characteristics were monitored by response surface analysis. The content of total nitrogen was high (around 1%) with fermentation at 51.7～57.5℃ after 10.2～16.4 hours, but rapidly decreased at higher temperatures (60℃ or over), while the R² of polynomial equation was 0.9185 (p＜0.05). The amino acid content rapidly decreased to approximately 600 mg% and less at high temperature (60℃ and over), and the R² was 0.9578 (p＜0.01). The free amino acids were affected more by fermentation time when fermentation temperature was lower, and the R² for total free amino acids was 0.8496 (p＜0.10). The R² for sweet free amino acids was 0.9144 (p＜0.05). According to the results of this study, the optimal conditions for anchovy sauce fermentation were predicted to be 52.5～56.9℃ and 13.3～16.4 hours, and the predicted values and actual values of each response variable were similar to each other when the fermentation was performed at a random point within the optimal range. Also, the comparison of the quality between the quick anchovy sauce and sauces currently on the market showed that the content of sweet amino acids was higher in the former than in the latter.

Background: Previous studies on Helicobacter pylori infection in mice have contributed to better understanding of the pathogenesis of chronic gastritis and gastric carcinoma. The aim of this study was to evaluate H. pylori colonization and subsequent inflammatory responses in the stomachs of C57BL/6 mice depending on inoculation number and the presence of high-salt diet. Methods: Eighty-four female mice with 4 weeks age were used in this study. The infected mice were gavaged with H. pylori strain Sydney-1 (SS1), and the uninfected mice were dosed with vehicle. In each of these groups, half of the mice were fed ona basal diet (0.25% salt) and the other half were fed on a high-salt diet (7.5% salt). The infected mice were inoculated 4 or 5 times, and infection status and degree of inflammation were checked by culture and histopathology, respectively, after 4 weeks. Gastric mucosal myeloperoxidase and tumor necrosis factor-alpha were measured by ELISA. Results: The overall infection rate was 95.2%; the infection rate after 5 inoculations (100%) was greater than that after 4 inoculations (91.3%). However, no differences in the degree of inflammation were found between 2 groups. The bacterial density was also significantly increased in mice that were on the high-salt diet and had been inoculated 5 times, respectively. Mean neutrophil infiltration in the infected group was 1.7±0.6 (1, minimal; 2, mild; 3, moderate; 4, marked). However, the high-salt diet was not increase the inflammatory grade in the infected group. Gastric mucosal myeloperoxidase and tumor necrosis factor-alpha levels did not increased by the high-salt diet and increased the number of inoculation. Conclusions: In spite of well colonization of H. pylori in the stomachs of C57BL/6 mice, the degree of subsequent inflammation was irrelevant to high-salt diet and frequent (5 times) inoculations.

BACKGROUND: Over the years, a great deal of effort has been focused on the design and synthesis of potent, linear peptide inhibitors targeting the polo-like kinase 1 (Plk1), which is critically involved in multiple mitotic processes and has been established as an adverse prognostic marker for tumor patients. Plk1 localizes to its intracellular anchoring sites via its polo-box domain, and inhibiting the Plk1 polo-box domain has been considered as an approach to circumvent the specificity problems associated with inhibiting the conserved adenosine triphosphate-binding pocket. The polo-box domain consists of two different binding regions, such as the unique, broader pyrrolidine-binding pocket and the conserved, narrow, Tyr-rich hydrophobic channel, among the three Plk polo-box domains (Plks 1-3), respectively. Therefore, the studies that provide insights into the binding nature of the unique, broader pyrrolidine-binding pocket might lead to the development of selective Plk1-inhibitory compounds. METHODOLOGY/PRINCIPAL FINDINGS: In an attempt to retain the monospecificity by targeting the unique, broader pyrrolidine-binding pocket, here, for the first time, a systematic approach was undertaken to examine the structure-activity relationship of N-terminal-truncated PLHSpTM derivatives, to apply a site-directed ligand approach using bulky aromatic and non-aromatic systems, and to characterize the binding nature of these analogues using X-ray crystallographic studies. We have identified a new mode of binding interactions, having improved binding affinity and retaining the Plk1 polo-box domain specificity, at the pyrrolidine-binding pocket. Furthermore, our data revealed that the pyrrolidine-binding pocket was very specific to recognize a short and bulky hydrophobic ligand like adamantane, whereas the Tyr-rich hydrophobic channel was specific with lengthy and small hydrophobic groups. CONCLUSION/SIGNIFICANCE: The progress made using our site-directed ligands validated this approach to specifically direct the ligand into the unique pyrrolidine-binding region, and it extends the applicability of the strategy for discovering selective protein-protein interaction inhibitors.

Here we report for the first time the synthesis of Histidine (His) derived lipo-amino acids having pendant lipid tails at N(τ)- and N(π)-positions on imidazole group of His and applied it into synthesis of lipo-peptides. The attachment of His-derived lipo-amino acid into the very short inactive cationic peptides endows potent antimicrobial activity against Gram-positive and Gram-negative bacteria without hemolytic activity. Furthermore, our designed His-derived lipo-peptidomimetics (HDLPs) consisting of two or three residues displayed strong anti-MRSA activity and protease stability as well as retained potent antimicrobial activity under high salt concentration. Our results demonstrate that the novel lipo-amino acid is highly flexible to synthesize and carry out the extensive structure-activity relationship (SAR) on lipo-antimicrobial peptidomimetics and represents a unique amenable platform for modifying parameters important for antimicrobial activity. Through this study, we proved that the discovery of His-derived lipo-amino acid and the corresponding HDLPs are an excellent candidate as a lead compound for the development of novel antimicrobial agents.

Since the bacterial resistance to antibiotics is increasing rapidly, numerous studies have contributed to the design and synthesis of potent synthetic mimics of antimicrobial peptides (AMPs). In an attempt to find the pharmacophore of short antimicrobial peptidomimetics through systematic tuning of hydrophobic and hydrophilic patterns, we have identified a set of short histidine-derived antimicrobial peptides (SAMPs) with potent and broad-spectrum activity. A combination of high antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), without hemolytic activity and proteolytic stability makes these molecules promising candidates for novel antimicrobial therapeutics.

Background Levodropropizine is an oral non-opioid anti-tussive drug used in treatment of cough. A new generic 60 mg capsule formulation of levodropropizine has recently been developed. Objectives The aim of this study was to assess the pharmacokinetics and bioequivalence of the test (capsule) formulation and reference (syrup) formulation of levodropropizine (60 mg) in healthy, fasted, male Korean volunteers. Methods This was a single-dose, randomized sequence, open-label, 2-period crossover study conducted in healthy male Korean volunteers in the fasted state at Kyung Hee University Medical Center (Seoul, Republic of Korea). A single oral dose of the test or reference formulation was followed by a 1-week washout period, after which subjects received the alternative formulation. Blood samples were collected at 0 (predose), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after study drug administration. Plasma concentration of levodropropizine was determined using a validated liquid chromatography tandem mass spectrometry (LCMS/ MS) method. The formulations were considered bioequivalent if the 90% CIs for C(max), AUC(0-12h) and AUC(0-∞) were within the predetermined bioequivalence range (80 - 125%, according to the guidelines of the Korea Food and Drug Administration (Korea FDA)). Tolerability was evaluated throughout the study based on vital sign measurements, laboratory analysis (blood biochemistry, hematology, hepatic function and urinalysis) and subject interviews concerning adverse events (AEs). Results A total of 36 male Korean subjects (mean (SD) age, 23.9 (2.4) years (range 19 - 30 years); height, 176.2 (6.1) cm (range 161 - 190 cm); weight, 69.8 (9.1) kg (range 54.0 - 92.2 kg); body mass index, 22.4 (2.1) kg/m2 (range 19.1 - 28.3 kg/m2)) was enrolled and completed the study. The mean values for C(max), t(max), AUC(0-12h), and AUC(0-∞) with the test formulation of levodropropizine were 331.51 ng/ml, 0.60 hours, 784.32 ng×h/ml, and 825.82 ng×h/ml, respectively; for the reference formulation, the values were 332.81 ng/ml, 0.44 hours, 726.46 ng×h/ml, and 769.46 ng×h/ ml, respectively. The 90% CIs for the logtransformed ratios of C(max) (92.74 - 111.24), AUC(0-12h) (104.31 - 113.67) and AUC(0-∞) (103.87 - 113.57) were within the predetermined range for the assumption of bioequivalence. No serious adverse events were reported. Conclusions This single-dose (60 mg) study found that the test (capsule) and reference (syrup) formulations of levodropropizine met the regulatory criterion for assuming bioequivalence in these healthy, fasted, male Korean subjects. Both formulations were well tolerated in the population studied. Korea FDA registration number: BED-1784.

Background: Much attention has been focused on the design and synthesis of potent, cationic antimicrobial peptides (AMPs) that possess both antimicrobial and anti-inflammatory activities. However, their development into therapeutic agents has been limited mainly due to their large size (12 to 50 residues in length) and poor protease stability. Methodology/Principal Findings: In an attempt to overcome the issues described above, a set of ultra-short, His-derived antimicrobial peptides (HDAMPs) has been developed for the first time. Through systematic tuning of pendant hydrophobic alkyl tails at the N(pi)- and N(tau)-positions on His, and the positive charge of Arg, much higher prokaryotic selectivity was achieved, compared to human AMP LL-37. Additionally, the most potent HDAMPs showed promising dual antimicrobial and anti-inflammatory activities, as well as anti-methicillin-resistant Staphylococcus aureus (MRSA) activity and proteolytic resistance. Our results from transmission electron microscopy, membrane depolarization, confocal laser-scanning microscopy, and calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via dissipation of the membrane potential by forming pore/ion channels on bacterial cell membranes. Conclusion/Significance: The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics.

A rapid, simple and fully validated LC-MS/MS method was developed and validated for the determination of megestrol acetate in human plasma using tolbutamide as an internal standard (IS) after one-step liquid-liquid extraction with methyl-tert-butyl-ether. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the transitions m/z 385.5 → 267.1 for megestrol acetate and m/z 271.4 → 155.1 for IS. Chromatographic separation was performed on a YMC Hydrosphere C18 column with an isocratic mobile phase, which consisted of 10 mm ammonium formate buffer (adjusted to pH 5.0 with formic acid)-methanol (60:40, v/v) at a flow rate of 0.4 mL/min. The achieved lower limit of quantitation (LLOQ) was 1 ng/mL (signal-to-noise ratio 10) and the standard calibration curve for megestrol acetate was linear (r 0.99) over the studied concentration range (1-2000 ng/mL). The proposed method was fully validated by determining its specificity, linearity, LLOQ, intra- and inter-day precision and accuracy, recovery, matrix effect and stability. The validated LC-MS/MS method was successfully applied for the evaluation of pharmacokinetic parameters of megestrol acetate after oral administration of a single dose 800 mg of megestrol acetate (Megace™) to five healthy Korean male volunteers under fed conditions.

An extension of our previously reported 3,4-dihydroquinazoline derivative is investigated. Oral anti-tumoral activity of 3,4-dihydroquinazoline derivative (KYS05090) as potent and selective T-type calcium channel blocker was in vivo evaluated against A549 xenograft in BALB/cnu/nu nude mice. The rate of tumor volume increment in mouse model with KYS05090-treated group was remarkably slower than that of control group. With respect to tumor weight, it exhibited 60% and 67% tumor growth inhibition through oral administration of 1 and 5 mg/kg of bodyweight, respectively, compared to control and was more potent than paclitaxel (53%). In addition, KYS05090 (10 and 50 mg/kg, po) was found to have a marked analgesic effect in acetic acid-induced writhing test, whereas it did not show any effect on hot plate test.

In the present study, we assessed the effects of gluco-obtusifolin, isolated from the seeds of Cassia obtusifolia L., and its aglycone, obtusifolin, on the learning and memory impairments induced by scopolamine using the passive avoidance and the Morris water maze tasks in mice. Gluco-obtusifolin (1, 2, and 4 mg/kg, p.o.) and obtusifolin (0.25, 0.5, 1, and 2 mg/kg, p.o.) significantly reversed scopolamine-induced cognitive impairments in the passive avoidance test (P

Ghrelin is an endogenous ligand for growth hormone (GH) secretagogue receptor 1a (GHS-R1a) and is produced and released mainly from the stomach. It was recently demonstrated that ghrelin can function as a neuroprotective factor by inhibiting apoptotic pathways. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity in rodents; previous studies suggest that activated microglia actively participate in the pathogenesis of Parkinson's disease (PD) neurodegeneration. However, the role of microglia in the neuroprotective properties of ghrelin is still unknown. Here we show that, in the mouse MPTP PD model generated by an acute regimen of MPTP administration, systemic administration of ghrelin significantly attenuates the loss of substantia nigra pars compacta (SNpc) neurons and the striatal dopaminergic fibers through the activation of GHS-R1a. We also found that ghrelin reduced nitrotyrosine levels and improved the impairment of rota-rod performance. Ghrelin prevents MPTP-induced microglial activation in the SNpc and striatum, the expression of pro-inflammatory molecules tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the activation of inducible nitric oxide synthase. The inhibitory effect of ghrelin on the activation of microglia appears to be indirect by suppressing matrix metalloproteinase-3 (MMP-3) expression in stressed dopaminergic neurons because GHS-R1a is not expressed in SNpc microglial cells. Finally, in vitro administration of ghrelin prevented 1-methyl-4-phenylpyridinium-induced dopaminergic cell loss, MMP-3 expression, microglial activation, and the subsequent release of TNF-alpha, IL-1beta, and nitrite in mesencephalic cultures. Our data indicate that ghrelin may act as a survival factor for dopaminergic neurons by functioning as a microglia-deactivating factor and suggest that ghrelin may be a valuable therapeutic agent for neurodegenerative diseases such as PD.