Pharmacokinetic and bioavailability studies of 5 mg mosapride tablets in healthy Korean volunteers.

AIM: Mosapride is a gastroprokinetic agent, a 5-HT4 receptor agonist and 5-HT3 receptor antagonist exhibiting no activity at dopamine D2, 5-HT1 and 5-HT2 receptors. This study was performed to compare basic pharmacokinetic (PK) characteristics of mosapride for Korean young adults and to evaluate the bioequivalence (BE) of two formulations of drugs mosapride. VOLUNTEERS AND METHODS: For pharmacokinetic and bioavailability of 5 mg mosapride tablets in healthy Korean adults, a randomized, two way, crossover bioequivalence study in 23 healthy Korean volunteers (M : F = 16 : 7) was conducted to compare bioavailability of two formulation of 5 mg mosapride citrate tablets, Moprid® (Chung Kun Dang Pharm Co., Ltd., Korea) as a test and Gasmotin® (Daewoong Pharm Co., Ltd., Korea) as a reference drug. Subjects were administered single dosage of 3 tablets of each formulation with 240 ml water after 10 h overnight fasting on 2 treatment days separated by 1-week washout period. Before and after dosing, blood sample were collected at 0, 0.25, 0.5, 0.8, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 h and analyzed by validated liquid chromatography- tandem mass spectrometry (LC-MS/ MS) in the range 1.28 - 192 ng/ml with the lowest limit of quantification of 1.28 ng/ml. RESULTS: Several PK characteristics were determined from the plasma samples, and data from reference and test formulations in the plasma were represented such as AUC0- t (184.4 vs. 179.6 ng×h/ml), AUC0-∞ (192.8 vs. 186.6 ng×h/ml), Cmax (98.9 vs. 84.4 ng/ ml), tmax (0.8 vs. 0.7 h), half-life (2.4 vs. 2.3 h), Ke (0.289 vs. 0.301), respectively. AUC0- t and Cmax were tested for bioequivalence after log-transformation of plasma data. PK characteristics with 90% confidence interval (CI) of test/reference ratio based on ANOVA analysis were 0.842 - 1.163 for AUC0-t and 0.753 - 1.088 for Cmax. PK characteristics with 90% CI were within the bioequivalence range of 80 - 125% of FDA statistical limit. Cmax with 90% CI were not within the bioequivalence range of 80 - 125% of FDA statistical limit. However, this result was assessed to bioequivalence in accordance with the "Bioequivalence Test Guidelines" outlined in No. 2005-31 of the KFDA. CONCLUSION: Therefore, both mosapride formulations were bioequivalent during fasting state in healthy Korean adults.

Collision of three histologically distinct endometrial cancers of the uterus.

A collision tumor is defined by the presence of two separate masses in one organ, which are pathologically distinct. We described a 70-yr-old patient who complained of abnormal vaginal bleeding with a collision tumor of the uterine corpus. The patient received total hysterectomy, bilateral salphingo-oophorectomy, bilateral pelvic-paraaortic lymphadenectomy, omentectomy, and intraperitoneal chemotherapy. The uterine corpus revealed three separate masses, which were located at the fundus, anterior and posterior wall. Each tumor revealed three pathologically different components, which were malignant mixed müllerian tumor, papillary serous carcinoma, and endometrioid adenocarcinoma. Among these components, only the papillary serous carcinoma component invaded the underlying myometrium and metastasized to the regional lymph node. Adjuvant chemotherapy and radiation therapy were performed. The patient is still alive and has been healthy for the last 8 yr. We have reviewed previously reported cases of collision tumors which have occurred in the uterine corpus.

Quantitative analysis of acyl-lysophosphatidic acid in plasma using negative ionization tandem mass spectrometry.

Analysis of acyl-lysophosphatidic acids (LPAs) has clinical importance as a potential biomarker for ovarian and other gynecological cancers or obesity from the point of view of prevention. Here we report a simple sample preparation and analytical method with high sensitivity and specificity for the early detection of gynecological cancers to improve the overall outcome of this disease. We established a novel quantification method for acyl-LPAs in plasma by electrospray negative ionization tandem mass spectrometry (MS-MS) using multiple reaction monitoring mode without conventional TLC step. Protein-bound lipids, acyl-LPAs in plasma were extracted with methanol/chloroform (2:1) containing LPA C(14:0) as internal standard under acidic conditions. Following back-extraction with chloroform and water, the centrifuged lower phase was evaporated and reconstituted in methanol and then analyzed. Using ESI-MS-MS with negative ionization MRM mode, all the species of LPAs were completely separated from plasma matrix without severe interference. For MRM mode, Q1 ions selected were m/z 409, 433, 435, 437 and 457 which corresponds to molecular mass [M-H](-) of C(16:0), C(18:2), C(18:1), C(18:0) and C(20:4) LPA, respectively. Q2 ions selected for MRM was m/z 79, phosphoryl product. Using MS-MS with MRM mode, all the species of LPAs were completely separated from plasma matrix without severe interference. This method allowed simultaneous detection and quantification of different species of LPAs in plasma over a linear dynamic range of 0.01-25 micromol/l. The method detection limit was 0.3 pmol/ml with correlation coefficient of 0.9983 in most LPAs analyzed. When applied to plasma from normal and gynecological cancer patients, this new method differentiated two different groups by way of total LPA level.

The relationship between coronary artery calcification and bone mineral density in patients according to their metabolic syndrome status.

BACKGROUND AND OBJECTIVES: The extent of coronary artery calcification (CAC) is closely related to total atherosclerotic plaque burden. However, the pathogenesis of CAC is still unclear. Conditions such as diabetes mellitus, renal failure, smoking, and chronic inflammation have been suggested to link vascular calcification and bone loss. In the present study, we hypothesized that bone loss can contribute to the pathogenesis of CAC in patients with the chronic inflammatory condition that accompanies metabolic syndrome (MetS). The objective of this study was to investigate the relationship between CAC and bone mineral density (BMD) in patients with MetS and in patients without MetS, by using coronary multidetector-row computed tomography (MDCT). SUBJECTS AND METHODS: Data from 395 consecutive patients was analyzed retrospectively. From the MDCT database, only those patients who underwent both coronary MDCT and dual-energy X-ray absorptiometry within an interval of one month, were selected. The presence of MetS was determined by the updated criteria as defined by the Third Adult Treatment Panel Report of the National Cholesterol Education Program. RESULTS: In patients with MetS, a significant correlation was found between CAC and age {odds ratio (OR)=1.139, 95% confidence interval (CI) 1.080 to 1.201, p<0.001}, CAC and male sex (OR=3.762, 95% CI 1.339 to 10.569, p=0.012), and CAC and T-score of L-spine (OR=0.740, 95% CI 0.550 to 0.996, p=0.047) using a forward multiple logistic regression analysis model including clinical variables of gender, age, lipid profile, body mass index, diabetes mellitus, hypertension, smoking, and BMD. But in patients without MetS, BMD by itself was not found to contribute to CAC. CONCLUSION: BMD was inversely correlated with CAC only in patients with MetS. This finding suggests that low BMD accompanied by MetS, may have significant clinical implications.

Laparoscopic surgery of ectopic gestational sac implanted in the cesarean section scar.

AIM: The feasibility and outcome of laparoscopic surgery for patients with ectopic pregnancy in the cesarean section scar was studied. METHODS: From January 2003 to June 2007, 7 of 9 patients diagnosed with ectopic pregnancy in a previous cesarean section scar underwent laparoscopic removal of the gestational sac at our department. A retrospective review of medical records of these patients was performed. RESULTS: In all of them, the ectopic gestational sac was successfully removed by laparoscopy without converting to laparotomy and the scar defect was repaired by intracorporeal sutures. The mean operation time was 98 minutes (range: 30 to 210 min) and mean hemoglobin drop after operation was 2.3 g/dL (range: 1.2 to 3.4 g/dL). The mean postoperative hospital stay was 4.3 days (range: 3 to 7 d). None of the patients required additional methotrexate administration postoperatively. CONCLUSIONS: Laparoscopic removal of ectopic gestational sac within a cesarean scar seems to be a feasible and safe procedure that might be considered as a treatment option.

Uterine leiomyoma with massive lymphoid infiltration: case report and review of the literature.

Uterine leiomyoma with massive lymphoid infiltration is a rare and unusual pathological finding. Only 13 cases have been reported in English literature. A case of uterine leiomyoma showing massive lymphoid infiltration in a 45-year-old woman is described. The tumor was relatively soft compared with usual leiomyomas. Microscopically, the tumor showed the typical features of leiomyoma with moderate to severe lymphocytic infiltrate consisting of mature lymphocytes, a few plasma cells and occasional histiocytes. This cellular infiltration was confined to the leiomyoma. Immunohistochemically, the diffusely infiltrated lymphoid cells were stained by antibodies to CD45RO, CD3 and CD8. Germinal centers were stained by antibodies to CD20 and CD79a. Some CD68+ histiocytes were seen. Lymphoid infiltration within the leiomyoma is a peculiar histological morphology, although the cause is not clear. The recognition of its distinct histological features is important to avoid possible confusion with differential diagnoses including malignant lymphoma, inflammatory pseudotumor and pyomyoma.