[Show abstract][Hide abstract] ABSTRACT: PURPOSE: The present study aimed to determine the predictive value of the heart-liver uptake ratio (H/L ratio) of rectally administered 201Tl scintigraphy for hepatic decompensation, which was conducted in 107 patients with cirrhosis. METHODS: We retrospectively assessed the predictive value of a noninvasive parameter, H/L ratio, for decompensation during a median follow-up period of 45.4 months using follow-up data from 1996 through 2008 for 107 patients with compensated cirrhosis. Logistic regression analysis and odds ratio estimates were used to estimate independent value of the H/L ratio on the risk of decompensation with 95% confidence intervals. RESULTS: At first visit, all subjects were confirmed as patients with compensated cirrhosis, 39 by liver biopsy and 68 by standard laboratory and radiological criteria. At end of the evaluation time, 81 patients remained compensated, whereas 26 patients decompensated as evidenced by ascites in 23, hepatic encephalopathy in 8, and variceal bleeding in 1 patient. First-visit parameters except bilirubin level, alanine aminotransferase (ALT), and H/L ratio and last visit parameters except ALT and aspartate aminotransferase-ALT ratio were significantly different between the 2 groups as ascertained by Wilcoxon rank sum test (P < 0.05). Among those parameters, we found that the last visit H/L ratio was a strongly reliable predictor of decompensation with an odds ratio estimates of 14.443, area under the receiver operating characteristic curve of 0.825, cutoff of 0.4, sensitivity of 73.1 %, and specificity of 71.6%. CONCLUSIONS: This evidence indicates that in patients with compensated cirrhosis, an increased H/L ratio at follow-up may be a useful predictive parameter showing a high risk of progression to a decompensated state.
Clinical nuclear medicine 01/2013; · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Selaginella tamariscina has been traditionally used in Korea for treating hematochezia, hematuria, and prolapse of the anus. The aim of this study was to evaluate the inhibitory effect of Selaginella tamariscina water extract (ST-WE) on osteoclast differentiation, and to determine the underlying molecular mechanism.
RAW264.7 cells were used as a model to examine receptor activator for the nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. Expression of osteoclastic genes and transcription factors was evaluated by real-time quantitative polymerase chain reaction (QPCR). Activation of the mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, and NF-κB were determined by Western blot analysis.
ST-WE significantly inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity and formation of multinucleated osteoclasts in RAW264.7 cells. ST-WE also significantly inhibited the RANKL-induced mRNA expression of TRAP, cathepsin K, and the d2 isoform of vacuolar ATPase V(0) domain (ATPv0d2) gene. In addition, ST-WE inhibited the RANKL-induced phosphorylation of ERK, JNK, and p38, phosphorylation of I-κB(α) and NF-κB p65, and the expression of transcription factors c-fos, Fra-2, and nuclear factor of activated T cells 1. Furthermore, ST inhibited the bone resorptive activity of osteoclasts.
ST-WE might have beneficial effects on bonedisease by inhibiting osteoclastogenesis and osteoclastic activity.
[Show abstract][Hide abstract] ABSTRACT: A simple, rapid and selective liquid chromatography method coupled with tandem mass spectrometry is developed and validated for the quantification of galantamine in human plasma using a commercially available compound, glimepride, as an internal standard (IS). Following simple one-step liquid-liquid extraction by ethyl acetate, the analytes are separated using an isocratic mobile phase consisting of acetonitrile and 0.01M ammonium acetate (95/5, v/v) on a reverse-phase C18 column and analyzed by tandem mass spectrometry in the multiple reaction monitoring mode using the transitions of respective (M + H)(+) ions, m/z 288.22 → 213.20 and m/z 491.17 → 352.30 for the quantification of galantamine and IS, respectively. The standard calibration curves show good linearity within the range of 4 to 240 ng/mL (r(2) = 0.9996, 1/x(2) weighting). The lower limit of quantification is 4 ng/mL. The retention times of galantamine and IS are 1.1 and 0.71 min, which showsthe high throughput potential of the proposed method. In addition, no significant metabolic compounds are found to interfere with the analysis. Acceptable precision and accuracy are obtained for the concentrations over the standard curve range. The validated method is successfully applied for pharmacokinetic and bioequivalence studies of 24 mg of a galantamine hydrobromide capsule in 32 healthy Korean subjects.
Journal of chromatographic science 06/2012; 50(9):803-9. · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nimesulide is a selective COX-2 inhibitor that is as effective as the classical non-acidic nonsteroidal anti-inflammatory drugs in the relief of various pain and inflammatory conditions, but is better tolerated with lower incidences of adverse effects than other drugs. After oral dose of 100 mg nimesulide to western subjects, a mean maximal concentration (C(max)) of 2.86 ∼ 6.5 µg/mL was reached at 1.22 ∼ 2.75 h and mean t(1/2β) of 1.8 ∼ 4.74 h. This study developed a robust method for quantification of nimesulide for the pharmacokinetics and suitability of its dosage in Korea and compared its suitability with other racial populations. Nimesulide and internal standard were extracted from acidified samples with methyl tert-butyl ether and analyzed by high-performance liquid chromatography with ultraviolet detection (HPLC-UV). The 28 healthy volunteers took 2 tablets of 100 mg nimesulide and blood concentrations were analyzed during the 24 h post dose. Several pharmacokinetic parameters were represented: AUC(0-infinity) = 113.0 mg-h/mL, C(max) = 12.06 mg/mL, time for maximal concentrations (T(max)) = 3.19 h and t(1/2β) = 4.51 h. These were different from those of western populations as follows: AUC was 14.5% and C(max) was 28% that of of Korean subjects and T(max) and t(1/2β) were also different. The validated HPLC-UV method was successfully applied for the pharmacokinetic studies of nimesulide in Korean subjects. Because the pharmacokinetics of nimesulide were different from western populations, its dosage regimen needs to be adjusted for Koreans.
Journal of chromatographic science 03/2012; 50(5):396-400. · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives: The stability of two kinds of solution of penicillin G potassium [PEN-K, 10K U/mL in 5% dextrose water, D5W and 50K U/mL in 0.9% sodium chloride in water, NS) into the intravenous infusion device, Accufuser ® , storage were evaluated at controlled temperature (CT, 4±2°C and RT, 25±2°C) during 6 weeks. Methods: Studies were performed using both NS (PEN-K 50K U/mL) and D5W (PEN-K 10K U/mL) injectable solutions. The resulting solutions were transferred to Accufuser ® infusion device for storage at CT or RT. Effects of period of stor-age (from 0 to 6 weeks) and temperature (CT and RT) on the physical appearance and concentrations of PEN-K were de-termined by visual clarity, pH and antibiotic concentrations by measurement with stability-indicating high-performance liquid chromatography (HPLC) method. Results: In NS (50 K U/mL) and D5W (10K U/mL) solutions, concentrations of PEN-K were slightly change and re-mained 94.18 and 83.42% at CT after 1 week, respectively. Otherwise, these were rapidly decreased with time and reached to 74.65 and 75.59% in NS (50K U/mL) and D5W (10K U/mL) solutions at RT after 48 h, respectively. Moderate decrement of pH was observed in cold storage and it was shown no significant changes at 6 weeks in the RT conditions. In CT, no significant changes in physical appearance or color of the solutions were observed during the study. Conclusion: Two kinds of PEN-K D5W(10K U/mL) and NS(50K U/mL) solution were shown different chemical stability with time in Accufuser ® infusion device without any significant physical change and retained about 70% of initial concen-tration after 48 h in RT and 80 % after 2 weeks in CT, respectively. We suggested that PEN-K solutions of 50K U/mL NS and 10K U/mL D5W in an Accufuser ® infusion device should be preferentially applicable only in CT for 48 h in clinical situations.
The Open Nutraceuticals Journal 01/2011; 411(125):125-129.
[Show abstract][Hide abstract] ABSTRACT: Increased activity of 11β-hydroxysteroid dehy-drogenase type 1 (11β-HSD-1) has been impli-cated in the development of the metabolic syn-dromes by amplification of local glucocorticoid ac-tions through regeneration of active glucocorticoid receptor. The present study was examined whether inhibition of 11β-HSD-1 by carbenoxolone (CBX), a non-selective 11β-HSD inhibitor, improved carbohy-drate metabolism in insulin resistant Otsuka Long-Evans Tokushima Fatty (OLETF) rats or not. Rats received subcutaneous CBX, twice a day [50 mg/kg bodyweight (b.w.)] or vehicle for 2 weeks, and then were evaluated fasting blood glucose levels, glucose tolerance, serum fasting insulin levels, and blood lipid levels in the both groups. The fast-ing blood glucose and insulin were lower in CBX-treated OLETF rats at 2 weeks than those of com-pared to day 0 and vehicle-treated OLETF rats at 2 weeks. Blood glucose fluctuations of the CBX-treated OLETF rats were more normal than those of vehicle-treated ones during intraperitoneal glucose tolerance tests. Blood concentrations of cholesterol and free fatty acids in the CBX-treated OLETF rats were lesser than those of vehicle-treated ones. The area under time-concentration curve (AUC 120 min) of blood glucose during the glucose tolerance test and of CBX-treated OLETF rats was significantly lower than that of the vehicle-treated ones, and insulinogenic index (ISI 30 min) was significantly different between CBX-and vehicle-treated groups. These results suggested that inhibition of 11β-HSD-1 by CBX might be im-proved carbohydrate metabolism and lipid profile in the insulin-resistant OLETF rats.
[Show abstract][Hide abstract] ABSTRACT: A liquid chromatography coupled to tandem mass spectrometry (LC-ESI/MS/MS) was validated to determine azelastine in human plasma. Azelastine and internal standard (IS, clomipramine) were separated using a mobile phase of acetonitrile:(5 mM)-ammonium acetate solution (70:30, v/v, pH=6.4) with flow rate of 0.25 mL/min over YMC C8 column. One mL of plasma was extracted by n-hexane: 2-propanol (97:3, v/v) and then injected into HPLC system after reconstitution by acetonitrile: (5 mM)-ammonium acetate (1:1, v/v) solution. Detection was carried out on API5000 MS system by multiple reactions monitoring mode. The ionization was optimized using ESI (+) and selectivity was achieved at m/z 382.2→112.2 for azelastine and m/z 315.3→228.0 for IS. Total run-time (<2.0 min) and linearity (10 (LLOQ) ~5000 pg/mL) were good. No endogenous compounds were found around the retention time. The inter- and intra-day precision and accuracy were 4.13~17.91% and 87.57~109.70%, respectively. This validated method was successfully applied to a bioequivalence study in 23 healthy Korean male volunteers from the blood samples taken up to 96 h after orally administered 2 tablets of 1 mg of reference and test formulations of azelastine in a double-blind, randomized, cross-over design. The mean peak plasma concentrations (Cmax ± SD) of 1.02 ± 0.37 and 1.10 ± 0.43 ng/mL were reached at 5.9 and 5.6 h for reference and test azelastine, respectively. The mean total area under the curve (AUC0-infinity) were 25.96 ± 10.84 and 28.24 ± 11.09 ng·h/mL for reference and test formulations, respectively. The reference and test azelastine formulations can be considered bioequivalent from the obtained pharmacokinetics by LC-ESI/MS/MS.
International journal of biomedical science : IJBS. 06/2010; 6(2):120-127.
[Show abstract][Hide abstract] ABSTRACT: The aquaporin (AQP) water channel is expected to play a decisive role of hyponatremia and water retention in cirrhotic patients.
Despite the importance of the water channel, however, previous findings vary widely when it concerns AQP2 of the kidneys in
subjects with cirrhosis. The purpose of this study was to investigate the expression of AQP2 in the distal renal tubule in
cirrhosis, and the presence of the nitric oxide-AQP2 signaling pathway as a possible vasopressin-aquaporin-independent pathway.
Sixty male Wister rats were assigned to six groups: (1) control; (2) TAA (thioacetamide); (3) TAA with nitric oxide donor;
(4) TAA with nitric oxide inhibitor; (5) TAA with HMG CoA reductase inhibitor; (6) TAA with tetrahydrobiopterin. Immunohistochemical
staining for AQP2, real-time polymerase chain reaction (PCR) for AQP2 and 3, citrulline assay, and renal cGMP concentration
were measured. The AQP2-positivity of cirrhotic rats were higher than the controls (P<0.05). The AQP2-positivity decreased in the nitric oxide donor group, but the proportion rose back up when the subjects
were injected with the nitric oxide inhibitor (P<0.05). The expression of AQP2 and AQP3 mRNA was also found to show an increase in the cirrhotic group as compared with
the normal controls (P<0.05). The cirrhotic group administered with nitric oxide donor showed a significant decline in the expression of the mRNA.
The control group’s cGMP concentration was lower than that of the cirrhotic group (P<0.05), but a comparison of the two groups injected with nitric oxide modulators, such as statin and BH4, did not show significant
differences in the cGMP concentration level. The expression of AQP2 of the kidneys increased in the cirrhotic rats. AQP2 had
relations to the activity changes of nitric oxide synthetase.
Digestive Diseases and Sciences 05/2010; 55(5):1296-1304. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Limaprost, a prostaglandin E1 analogue, with a strong vasodilatory and antiplatelet activity has been used to release from the symptoms of thromboangiitis obliterans (TAO), which is more prevalent in Korea and Japan, and lumbar spinal canal stenosis (LSCS). In spite of many uses of limaprost, the pharmacokinetics (PK) of it has not been studied in the Korean population. Therefore, a preliminary PK study was designed at a clinical oral dosage of 30-microg limaprost in 5 healthy Korean volunteers. Blood samples were obtained at 14 consecutive time points for 12 hours after dosing and analyzed by liquid chromatography-tandem mass spectrometry with electrospray ionization (LC-ESI/MS/ MS) at a very low detection limit of 0.5 pg/mL of limaprost in human plasma with considerably short run time (18 minutes). Pharmacokinetic characteristics resulted in ''time for maximal concentrations (T(max) 0.5 hour),'' ''elimination half-life (T(1/2) 1.64 hours),'' ''maximal concentration (C(max) 13.37 pg/mL),'' ''area under the curve (AUC(12 hours) 18.60 pg . h/mL),'' ''AUC extrapolated to infinity (AUC(infinity) 22.98 pg . h/mL),'' ''extrapolation (AUC(infinity - 12 hours)/AUC(infinity) 0.15%),'' ''elimination rate constant (k(e) 0.68 h(-1)),'' ''systemic clearance (CL 1.77 L/h),'' and ''mean residence time (MRT 1.74 hours).'' These results showed that orally administered 30-microg limaprost was rapidly and highly absorbed, and it was considerably eliminated fast from the blood stream in the healthy Korean volunteers.
Clinical and Applied Thrombosis/Hemostasis 10/2009; 16(3):326-33. · 1.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Alendronate sodium is a Bisphosphonate drug used to treat and prevent osteoporosis and several other bone diseases. A new formulation has been developed and is currently awaiting regulatory approval, pending findings on bioequivalence.
The aims of the present study were to compare the bioavailability and pharmacokinetic (PK) properties, and to determine the bioequivalence, of a test and reference formulation of alendronate sodium 70 mg in a healthy Korean adult male population.
This open-label, randomized, 2-sequence, 2-period crossover study was carried out at Hanyang University Medical Center (Seoul, Republic of Korea). Healthy Korean adult male volunteers were randomly assigned to receive a single 70-mg dose of the test or reference formulation of alendronate sodium, administered with 240 mL of water, followed by a 7-day washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Serial blood samples were collected and adverse events were monitored by a clinical investigator via observation, personal interview, and vital signs (blood pressure, heart rate, and body temperature) over a 7-hour period (at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, and 7 hours) after drug administration. Plasma alendronate sodium concentrations were determined using a validated high-performance liquid chromatographic-postcolumn fluorescence derivatization method, with visible detection in the range of 2 to 100 ng/mL and lower limit of quantification set at 2 ng/mL. PK properties, including AUC(0-t), AUC(0-infinity), C(max), T(max), t(1/2), and the elimination constant (k(e)), were determined using non-compartmental analysis. The formulations were considered bioequivalent if the 90% CI ratios for C(max) and AUC were within the predetermined interval of 80% to 125%, the regulatory definition set by the US Food and Drug Administration (FDA).
Twenty-three healthy male volunteers (mean [SD] age, 23.5 [2.0] years [range, 19-28 years]; height, 175.9 [5.4] cm [range, 162.0-185.0 cm]; and weight, 71.2 [9.5] kg [range, 61-96 kg]) were included in the study. No period or sequence effects were detected. The 90% CIs for the corresponding ratios of AUC(0-t), AUC(0-infinity) and C(max) were 84.97 to 114.47, 86.09 to 115.59, and 82.37 to 110.71, respectively. Additionally, the mean (range) of T(max) was 1.09 hours (0.5-2.0 hours), and the mean (SD) of t(1/2) and k(e) were 2.04 (0.97) hours and 0.34 (0.71) hour, respectively. The values for the test and reference formulations were within the FDA bioequivalence definition interval of 80% to 125%. No adverse events were reported in this study.
Single doses of these formulations of alendronate sodium 70 mg met the criteria for bio-equivalence. No statistically significant differences in AUC(0-t), AUC(0-infinity), and C(max) were found in this healthy Korean adult male population.
[Show abstract][Hide abstract] ABSTRACT: A rapid and validated method for analysis of levosulpiride in human plasma using liquid chromatography coupled to tandem mass spectrometry was developed. Levosulpiride and tiapride (IS, internal standard) were extracted from alkalized plasma samples with ethylacetate and separation by RP-HPLC. Detection was performed by positive ion electrospray ionization in multiple-reaction monitoring mode, monitoring the transitions m/z 342.1 --> m/z 112.2 and m/z 329.1 --> m/z 213.2, for quantification of levosulpiride and IS, respectively. The standard calibration curves showed good linearity within the range of 2-200 ng/mL (r(2) > or = 0.9990). The lower limit of quantitation was 2 ng/mL. The retention times of levosulpiride (0.63 min) and IS (0.66 min) presented a significant time saving benefit of the proposed method. No significant metabolic compounds were found to interfere with the analysis. This method offered good precision and accuracy and was successfully applied for the pharmacokinetic and bioequivalence study of a 25 mg of levosulpiride tablet in 24 healthy Korean volunteers.
[Show abstract][Hide abstract] ABSTRACT: A rapid and highly sensitive liquid chromatography/electrospray ionization tandem mass spectrometric method (LC/ESI-MS/MS) for itraconazole determination in human plasma was validated and applied to pharmacokinetic and bioequivalence study in humans. In a randomized crossover design with a 1-week period, each subject received a 200 mg itraconazole capsule. The analytical procedures involved a less time-consuming, simple protein precipitation with methyl t-butyl ether and separation by HPLC. The ionization was optimized using electrospray ionization (ESI) with positive ion mode and selectivity was achieved by MS/MS analysis, m/z 705.3 --> 392.4 and m/z 374.3 --> 141.0 for itraconazole and internal standard (IS), respectively. The standard calibration curves showed good linearity within the range of 1 (LLOQ) to 500 ng/mL for itraconazole in human plasma with a correlation coefficient r > 0.9952. The retention times of itraconazole (0.9 min) and IS (0.84 min) suggest the high throughput of the proposed method. No significant metabolic compounds were found to interfere with the analysis. The coefficient of variation values of both intra- and inter-day were below 13.7% and 10.9%, respectively. Intra- and inter-day accuracies were 95.6-108.2% and 86.6-117.5%, respectively. This method was successfully applied for pharmacokinetic and bioequivalence study in 24 healthy human subjects by analysis of blood samples taken up to 72 h after an oral dose of 200 mg of itraconazole.
[Show abstract][Hide abstract] ABSTRACT: A highly sensitive and rapid method for the analysis of isradipine in human plasma using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was developed. The procedure involves a simple liquid-liquid extraction of isradipine and amlodipine (IS, internal standard) with methyl-t-butyl ether after alkaline treatment and separation by RP-HPLC. Detection was performed by positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 372.1-->m/z 312.2 and m/z 408.8-->m/z 237.9, for quantification of isradipine and IS, respectively. The standard calibration curves showed good linearity within the range of 10 to 5000 pg/mL (r(2)>or=0.9998). The lower limit of quantitation (LLOQ) was 10 pg/mL. The retention times of isradipine (0.81 min) and IS (0.65 min) suggested the potential for high throughput of the proposed method. In addition, no significant metabolic compounds were found to interfere with the analysis. This method offered good precision and accuracy and was successfully applied for the pharmacokinetic and bioequivalence studies of 5 mg of sustained-release isradipine in 24 healthy Korean volunteers.
Journal of Chromatography B 12/2008; 877(1-2):59-64. · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aceclofenac is a phenylacetic acid derivative with analgesic and anti-inflammatory properties and an improved gastrointestinal tolerance compared with other NSAIDs, such as diclofenac.
This study was conducted to compare the bioavailability of 2 branded formulations of aceclofenac 100 mg (test and reference) marketed in Korea. Methods: This single-dose, randomized, open-label, 2-period crossover study in healthy Korean adult volunteers was conducted at Hanyang University Medical Center (Seoul, Republic of Korea). Subjects received 1 tablet of each aceclofenac 100-mg formulation. Study drugs were administered with 240 mL of water after a 10-hour overnight fast on each of 2 treatment days separated by a 1-week washout period. After study drug administration, serial blood samples were collected over a period of 12 hours. Plasma was analyzed for aceclofenac concentration using a validated high-performance liquid chromatography method with visible detection in the range of 0.1 to 20 microg/mL, with a lower limit of quantitation of 0.1 microg/mL. Several pharmacokinetic (PK) parameters, including C(max), T(max), t(1/2), AUC(0-t), AUC(0-infinity), and k(e), were determined from the plasma concentrations of the 2 aceclofenac formulations. C(max), AUC(0-t), and AUC(0-infinity) were used to test for bioequivalence after log-transformation of plasma data. The predetermined, regulatory range of 90% CI for bioequivalence was 0.80 to 1.25.
A total of 24 subjects were enrolled (20 men, 4 women; mean [SD] age, 23.5 [1.4] years; mean [SD] weight, 68.1 [11.5] kg). No significant differences were found based on analysis of variance, with mean values and 90% CIs of test/reference ratios for these parameters as follows: C(max), 10.57 versus 9.79 microg/mL (0.961-1.225); AUC(0-t), 19.95 versus 19.93 microg x h/mL (0.937-1.037); and AUC(0-infinity), 20.75 versus 20.48 microg x h/mL (0.949-1.049).
In these healthy Korean volunteers, results from the PK analysis suggested that the test and reference formulations of aceclofenac 100-mg tablets were bioequivalent, based on the regulatory definition.
[Show abstract][Hide abstract] ABSTRACT: A rapid, simple and validated liquid chromatography coupled to tandem mass spectrometric method (LC-MS/MS) for topiramate analysis in human plasma has been applied to pharmacokinetic and bioequivalence studies in 24 healthy male Korean volunteers. The procedure involves a simple liquid extraction of topiramate and prednisone (internal standard) with acetonitrile and separation by HPLC equipped with a Capcell Pak C18 column using acetonitrile-0.1% triethylamine (80:20, v/v) as a mobile phase. Detection was carried out on an API 2000 MS system by multiple reactions monitoring mode. The ionization was optimized using ESI(-) and selectivity was achieved by MS/MS analysis, m/z 338.0 --> 77.5 and m/z 357.1 --> 327.2 for topiramate and prednisone, respectively. The method had a total run time of 2.5 min and showed good linearity over a working range of 20-5000 ng/mL in human plasma with a lower limit of quantification of 20 ng/mL. No metabolic compounds were found to interfere with the analysis. The inter-day and intra-day accuracy were in the ranges of 99.24-116.63 and 93.45-108.68%, respectively, and inter-day and intra-day precisions were below 6.24 and 5.25%, respectively. This method was successfully applied for pharmacokinetic and bioequivalence studies by analysis of blood samples taken up to 96 h after an oral administration of 100 mg of topiramate in 24 healthy Korean volunteers.
[Show abstract][Hide abstract] ABSTRACT: Antidiabetic effect of Korean red ginseng (RG) processed by puffing in streptozotocin (STZ)-induced diabetic (DM) rats was investigated. Five week-old SD rats were divided into four groups; normal control (NC) group, DM group, red ginseng (RG) group and puffed red ginseng (PG) group. The RG and PG groups were orally provided with RG or PG dissolved in water (500 mg/kg) respectively for seven weeks after single injection of STZ (50 mg/kg, i.v.) followed by identification of DM. NC group received saline vehicle instead of STZ. At the end of feeding of RG or PG, the changes of fasting blood glucose, serum insulin and amylase level and serum lipid profiles were evaluated. Also, oral glucose tolerance test (OGTT), comet assay and histopathological examination were performed. At 7th week, the fasting blood glucose levels of the RG and PG groups were reduced compared to the DM group by 11.54% and 20.22%, respectively. The result of OGTT did not show significant differences among DM and two red ginseng groups. While serum insulin and TG levels were predominantly improved in PG group (p
Journal of the Korean Society of Food Science and Nutrition 01/2008; 37(6):701-707.
[Show abstract][Hide abstract] ABSTRACT: A sensitive validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for gabapentin (GB) in human plasma has been developed and applied to pharmacokinetic (PK) and bioequivalence (BE) studies in human. In a randomized crossover design with a 1-week period, each subject received a 300 mg GB capsule. The procedure involves a simple protein precipitation with acetonitrile and separated by LC with a Gemini C(18) column using acetonitrile-10 mm ammonium acetate (20:80, v/v, pH 3.2) as mobile phase. The GB and internal standard [(S)-(+)-alpha-aminocyclohexanepropionic acid hydrate] were analyzed using an LC-API 2000 MS/MS in multiple reaction monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved using MS/MS analysis, m/z 172.0 --> 154.0 and m/z 172.0 --> 126.0 for GB and IS, respectively. The assay exhibited good linearity over a working range of 20-5000 ng/mL for GB in human plasma with a lower limit of quantitation of 20 ng/mL. No endogenous compounds were found to interfere with the analysis. The accuracy and precision were shown for concentrations over the standard ranges. This method was successfully applied for the PK and BE studies by analysis of blood samples taken up to 36 h after an oral dose of 300 mg of GB in 24 healthy volunteers.
[Show abstract][Hide abstract] ABSTRACT: Chromium picolinate (CrP) supplementation has been studied as a potential therapy of insulin resistance and lipid abnormalities. There have been some reports involving chromium supplementation in patients with diabetes, but the results are varied. The present study was conducted to assess the effects of CrP on insulin sensitivity and body weight in Goto-Kakizaki (GK) diabetic rats. We supplemented normal Sprague-Dawley (SD) rats and GK diabetic rats with supplemental CrP, 100 mg/kg/day once a day for 4 weeks. In the normal SD rats, the mean body weight of the control group increased by 50.5%, whereas that of the CrP-treated group increased by 65.9% (P < 0.05 vs control). Similarly, in the diabetic GK rats, CrP supplementation showed increased weight gain compared to the control group (133.4% vs 119.6% of the baseline weight, P < 0.01). Glucose tolerance tests (GTT) [ip injection of glucose; 2 g/kg] and insulin sensitivity tests [SQ injection of insulin (5 U/kg) plus ip injection of glucose (30 min after insulin injection)] were conducted. During insulin sensitivity tests at the end of treatment, the glucose levels were significantly lower in CrP-treated rats compared with the control rats (AUC0-->120; 113.1 +/- 32.0 vs 170.5 +/- 49.0 mg-min/mL, P < 0.05). During GTTs, the glucose levels and insulin concentrations in the CrP-treated rats were not different from those in the control rats. The results of these studies suggest that CrP supplementation in GK diabetic rats leads to increase of weight gain and improvement of insulin sensitivity. This raises the possibility that CrP supplementation can be considered to improve carbohydrate metabolism in patients with type 2 diabetes mellitus.
Journal of Trace Elements in Medicine and Biology 02/2004; 17(4):243-7. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chromium (Cr) is essential for the regulation of insulin action, and Cr supplementation has been studied as a potential therapy of insulin resistance and lipid abnormalities. Corticosteroid treatment is well known to cause the abnormality of carbohydrate metabolism. Recently, it has been reported that corticosteroid increases urinary loss of Cr, and Cr supplementation recovers steroid-induced diabetes mellitus. In this experiment, rats were treated daily with dexamethasone (DEX) (0.2 mg/kg, intraperitoneal [IP]) for the first 7 days and were further treated with DEX plus either chromium picolinate (CrP, 30 mg/kg/d) orally or a placebo for a period of 14 days. At the end of experiment (D21), the control rats, which were treated only with DEX weighed 320 g (80% of initial weight) on average, but CrP-treated rats weighed 364 g (91% of initial weight. P <.05). Glucose tolerance tests (GTTs) and insulin sensitivity tests were conducted. During insulin sensitivity tests, the area under the curve (AUC(0-->120)) of the time-glucose concentrations curves in CrP-treated group were decreased compared with those in the control group (271.4 +/- 74.9 v 1,097.4 +/- 722.2 mmol/L/min, P <.01). Fasting serum insulin levels in CrP-treated rats were clearly decreased by 46.9% compared with those in the control group (0.52 +/- 0.19 v 0.98 +/- 0.36 nmol/L, P <.05). During the GTTs, the AUC(0-->120) for time-glucose concentrations curves in CrP-treated group was not significantly different from the control group, but the AUC(0-->120) of serum insulin concentrations in the CrP-treated group were 55.8% lower than those in the control group (123.1 +/- 42.5 v 278.2 +/- 59.1 nmol/L/min, P <.01). The mean AUC(0-->120) of time-cholesterol concentration curves during GTTs did not significantly differ between the 2 groups (867.6 +/- 155.2 v 827.7 +/- 94.3 mmol/L/h, P = not significant [NS]). In contrast, 1-hour and 2-hour plasma triglycerides were significantly lower in the CrP-treated group, and the mean AUC of the time-triglyceride curve was significantly lower in CrP-treated group than in the control group (3.4 +/- 0.5 v 5.9 +/- 1.3 mmol/L/h, P <.05). We suggest that Cr supplementation in DEX-treated rats can relatively reverse a catabolic state and increase insulin sensitivity. Our results support the hypothesis that Cr supplementation can be considered to improve carbohydrate and lipid metabolism in patients receiving corticosteroid treatment.