Ibandronate (a bisphosphonate) is commonly used as an treatment of osteoporosis in combination with vitamin D. Monthly DP-R206-a novel, fixed-dose combination tablet (150 mg ibandronate/24,000 IU vitamin D3)-was recently developed to enhance patient compliance. This open, randomized, two-period crossover study was conducted to compare the pharmacokinetics of ibandronate when administered as DP-R206 or 150 mg ibandronate to healthy adult volunteers. Each volunteer was randomly allocated to receive single-dose DP-R206 or ibandronate with a 28-day washout period between treatments. Blood samples were assessed using pharmacokinetic analysis. Plasma ibandronate concentrations were determined using liquid chromatography-tandem mass spectrometry. Safety and tolerability assessments were performed throughout the study. In total, 103 participants received the study drugs and 72 participants completed the study. The geometric mean ratios (DP-R206/ibandronate) of the maximum concentration (C(max)) and the area under the plasma concentration time curve from time zero to the last concentration (AUC(last)) values were 0.959 (90% CI: 0.820-1.120) and 0.924 (90% CI: 0.805-1.060), respectively. The frequencies of adverse events (AEs) and drug reactions were similar between treatment groups, and all AEs were recovered without sequalae. Ibandronate pharmacokinetics, tolerability, and safety are comparable when administered to healthy individuals, regardless if administered as DP-R206 or ibandronate.
Adult* ; Cross-Over Studies ; Humans ; Mass Spectrometry ; Osteoporosis ; Patient Compliance ; Pharmacokinetics ; Plasma ; Vitamin D ; Vitamins* ; Volunteers

BACKGROUND: This clinical study was conducted to compare pharmacokinetics of eperisone and aceclofenac of HCP1104, a new fixed dose combination drug with those in co-administration of eperisone 50 mg and aceclofenac 100 mg. The study used a partial replicated study design to characterize intra-subject variability of eperisone when co-administrated with aceclofenac. METHODS: A partial replicated crossover design was employed in 30 subjects. Each subject received a single dose of co-administration of eperisone 50 mg and aceclofenac 100 mg on two occasions and a single dose of 1 capsule of HCP1104. Blood samples were obtained for 24 hrs after dosing, and plasma was assayed for eperisone and aceclofenac by Liquid chromatography-electrospray ionization-mass spectrometry. RESULTS: Using an average bioequivalence criterion, the 90 % confidence limits for Ln-transformed Cmax and AUClast for aceclofenac fell wihin the acceptable range of 80 - 125 %. Point estimates of eperisone AUClast and Cmax were 1.0152 and 1.0490, respectively and the 90 % confidence interval for Cmax was 0.8499 - 1.3025. The within-subject coefficient of variation of Cmax for the reference was 50.198 %. Acceptance range for eperisone Cmax based on new bioequivalence guidance for highly variable drugs was extended to 0.6984 - 1.4319. CONCLUSION: The extent of exposure and rate of absorption of both eperisone and aceclofenac with a single dose of HCP1104 capsule were equivalent to those with co-administration of a marketed eperisone 50 mg tablet and a marketed aceclofenac 100 mg tablet under fasting conditions in healthy adult males.
Absorption ; Adult ; Cross-Over Studies* ; Fasting ; Humans ; Male ; Pharmacokinetics* ; Plasma ; Spectrum Analysis ; Therapeutic Equivalency*

Vitamin E is the most important lipid-soluble antioxidant in humans. Although alpha-tocopherol is suggested that it has protective effect from many diseases, little is known about the prevention of occludin alteration in tight junction of blood-brain barrier (BBB) under pathologic insults producing reactive oxygen species (ROSs). In this study, the effects of alpha-tocopherol on H2O2-induced tight junction occludin were studied. Primary culture of rat brain microvessel endothelial cells was investigated with confocal microscopy, Western blot, and cell viability assay. Alpha-tocopherol had no apparent cytotoxicity up to 2.8 mM. The preincubation with alpha-tocopherol suppressed the H2O2-induced cytotoxicity in Alamar Blue assay and phase contrast microscopy. In confocal laser microscopy and Western blot, H2O2-induced loss of occludin was suppressed by preincubation with alpha-tocopherol. The present findings provide evidence that alpha-tocopherol may be beneficial for cellular protection from pathologic insults. Since alpha-tocopherol was demonstrated to have far fewer adverse effects, it would become a noteworthy nutrient or drug for the treatment of neurodegenerative diseases.
alpha-Tocopherol* ; Animals ; Blood-Brain Barrier* ; Blotting, Western ; Brain ; Cell Survival ; Endothelial Cells ; Humans ; Microscopy, Confocal ; Microscopy, Phase-Contrast ; Microvessels ; Neurodegenerative Diseases ; Occludin* ; Rats ; Reactive Oxygen Species ; Tight Junctions* ; Vitamin E ; Vitamins

OBJECTIVE: To evaluate how resection margin involvement after LLETZ affect treatment of CIN and microinvasive cervical cancer, and several factors affecting the resection margin involvement. METHOD: Retrospective analysis was performed in 160 patients that underwent LLETZ at Gachon Medical College, Gil Medical Center from March, 1997 to September , 1998. The several factors affecting the resection margin involvement were analyzed. RESULT: The following results were obtained. 1. 127 patients were diagnosized finally with CIN, 30 patients with microinvasive SCC and 3 patients with chronic inflammation. 2. The rate of the negative resection margin involvement was 81% and that of the positive was 19%. 3. No case among 129 cases with the negative resection margin had residual lesion, but 9 cases among 31 cases with the positive resection margin had residual lesion. As a whole, the rate of residual lesion was 6.2%. 4. In CIN, 3 cases of 19 cases with the positive resection margin had residual lesion, but none with the negative resection margin had. 5. The degree of histopathology, glandular involvement, menopause, colposcopic evaluation were correlated with the resection margin involvement but delivery mode and HPV infection not correlated. CONCLUSION: LLETZ is a enough method to reduce unnecessary hysterectomy in the treatment of CIN, if followed up, in spite of the positive resection margin because of low rate of lesidual lesion, and is a effective method in the treatment of microinvasive cervical cancer when the case with negative resection margin and no lymphovascular invasion was followed up.
Female ; Humans ; Hysterectomy ; Inflammation ; Menopause ; Retrospective Studies ; Uterine Cervical Neoplasms

Indobufen (Ibustrin®), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using NONMEM® and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0–128 mg/L. Collagen-induced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid I(max) model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or R-indobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently.
Blood Platelets ; Colon, Sigmoid ; Healthy Volunteers ; Humans ; In Vitro Techniques ; Plasma ; Platelet Aggregation ; Platelet-Rich Plasma ; Treatment Outcome

BACKGROUND: Letrozole is an oral non-steroidal inhibitor of the aromatase enzyme, which has proven to be a useful drug against breast cancer. METHODS: This single-dose, randomized 2 x 2 crossover study was conducted in healthy male volunteers. Participants of each sequence group (each 13 volunteers for sequence group) received, in randomized sequence, a single oral 2.5-mg dose of generic letrozole (test) or branded letrozole (reference). Each treatment period was separated by a 5-week washout period. Blood samples were collected for up to 312 hours after drug administration, and drug concentrations were determined using validated LC/MS-MS. Pharmacokinetic properties were obtained using noncompartmental analysis. Drug tolerability was assessed throughout the study, using measurements of vital signs, physical examination, clinical chemistry testing, EKG, and interviews. RESULTS: A total of 26 subjects completed the study. The geometric mean ratios (90% CI) of Cmax and AUClast were 0.92 (0.85 - 0.99) and 1.01 (0.97 - 1.04), respectively. No serious AEs were reported, and there were no clinically significant differences between test and reference groups. CONCLUSION: The findings from this study suggest bioequivalence between two formulations of letrozole in healthy male volunteers. The safety profile of two formulations had similar characteristics.
Aromatase ; Breast ; Clinical Chemistry Tests ; Cross-Over Studies ; Electrocardiography ; Humans ; Male ; Nitriles ; Physical Examination ; Therapeutic Equivalency ; Triazoles ; Vital Signs

PURPOSE: This study aimed to establish a large-scale database of patients with gastric cancer to facilitate the development of a national-cancer management system and a comprehensive cancer control policy. MATERIALS AND METHODS: An observational prospective cohort study on gastric cancer was initiated in 2010. A total of 14 cancer centers throughout the country and 152 researchers were involved in this study. Patient enrollment began in January 2011, and data regarding clinicopathological characteristics, life style-related factors, quality of life, as well as diet diaries were collected. RESULTS: In total, 4,963 patients were enrolled until December 2014, and approximately 5% of all Korean patients with gastric cancer annually were included. The mean age was 58.2±11.5 years, and 68.2% were men. The number of patients in each stage was as follows: 3,394 patients (68.4%) were in stage IA/B; 514 patients (10.4%), in stage IIA/B; 469 patients (9.5%), in stage IIIA/B/C; and 127 patients (2.6%), in stage IV. Surgical treatment was performed in 3,958 patients (79.8%), endoscopic resection was performed in 700 patients (14.1%), and 167 patients (3.4%) received palliative chemotherapy. The response rate for the questionnaire on the quality of life was 95%; however, diet diaries were only collected for 27% of patients. CONCLUSIONS: To provide comprehensive information on gastric cancer for patients, physicians, and government officials, a large-scale database of Korean patients with gastric cancer was established. Based on the findings of this cohort study, an effective cancer management system and national cancer control policy could be developed.
Cohort Studies* ; Diet ; Drug Therapy ; Humans ; Korea ; Male ; Occupational Groups ; Prospective Studies* ; Quality of Life ; Stomach Neoplasms*

PURPOSE: The prognosis for patients with stage IV gastric cancer is very poor. However, recently, some studies have reported benefits from a gastric resection for metastatic gastric cancer. This clinical study was performed to evaluate the effectiveness of a noncurative gastrectomy in treating stage IV gastric cancer with hepatic metastasis. MATERIALS AND METHODS: A retrospective analysis was performed on 98 gastric cancer patients who had undergone gastric resection, in spite of hepatic metastasis, between January 1990 and December 1996 at the Department of Surgery in 11 General Hospitals in Korea. RESULTS: The average age was 58 years old, and the male-to-female ratio was 69: 29. The laboratory tests were unable to predict hepatic metastasis. In 54 cases, hepatic metastasis was not identified before the surgery. The most common location of gastric cancer was antrum (72 cases). The most common gross type was Bonmann type III (78 cases). The serosa-exposed cases were 80. The peritoneal seeding was combined in 17 cases. A total gastrectomy was performed in 18 cases and a distal gastrectomy in 80. Lymph-node dissection was performed in 23 Dl, and 51 D2 cases. Hepatic resection was performed in 36 cases, The frequent histologic types were moderately differentiated and poorly differentiated tubular adenocarcinoma. Postoperative adjuvant chemotherapy was done in 70 cases. The complication rate (7%) was low. The median survival time was 15 months, with mean survival time of 18 months. The 2-year and 3-year survival rates were 23%, and 7%, respectively. In the univariate analysis, good survival was closely related to limitation of hepatic metastasis to one lobe, a few metastases to both lobes, negativity of peritoneal seeding and lymph node dissection more than D2 (p<0.05), CONCLUSIONS: An aggressive gastric resection for stage IV gastric cancer with hepatic metastasis might be beneficial in lengthening the survival period. A prospective study is needed, especiaUy one with an exact evaluation and analysis of the quality of life between the gastrectomy and nonresection groups.
Adenocarcinoma ; Chemotherapy, Adjuvant ; Gastrectomy* ; Hospitals, General ; Humans ; Korea ; Lymph Node Excision ; Middle Aged ; Neoplasm Metastasis* ; Prognosis ; Quality of Life ; Retrospective Studies ; Stomach Neoplasms* ; Survival Rate