Comparison of pharmacokinetics and safety characteristics between two olopatadine hydrochloride 5 mg tablet formulations in healthy Korean subjects

Histamine acts by binding to four histamine receptors (H1 to H4), of which the H1 is known to participate in dilate blood vessels, bronchoconstriction, and pruritus. Olopatadine hydrochloride blocks the release of histamine from mast cells and it inhibits H1 receptor activation. Olopatadine hydrochloride is anti-allergic agent that is effectively used. The object of this study had conducted to compare the pharmacokinetics (PKs) and safety characteristics between olopatadine hydrochloride 5 mg (test formulation) and olopatadine hydrochloride 5 mg (reference formulation; Alerac® ) in Korean subjects. This study had conducted an open-label, randomized, fasting condition, single-dose, 2-treatment, 2-period, 2-way crossover. Subjects received single-dosing of reference formulation or test formulation in each period and blood samples were collected over 24 hours after administration for PK analysis. A wash-out period of 7 days was placed between the doses. Plasma concentration of olopatadine were determined using liquid chromatography-tandem spectrometry mass (LC-MS/MS). A total of 32 subjects were enrolled and 28 subjects completed. There were not clinical significantly different in the safety between two treatment groups for 32 subjects who administered the study drug more than once. The geometric mean ratio of test formulation to reference formulation and its 90% confidence intervals for The peak plasma concentration (Cmax ) and the areas under the plasma concentration–time curve from 0 to the last concentration (AUClast ) were 1.0845 (1.0107–1.1637) and 1.0220 (1.0005–1.0439), respectively. Therefore, the test formulation was bioequivalent in PK characteristics and was equally safe as the reference formulation.

Pharmacokinetic comparison of two bazedoxifene acetate 20 mg tablet formulations in healthy Korean male volunteers

Bazedoxifene, used as bazedoxifene acetate, is a selective estrogen receptor modulator that selectively affects the uterus, breast tissue, bone metabolism, and lipid metabolism by antagonizing or enhancing estrogens in the estrogen receptor in the tissue. This study was conducted as an open, randomized, two-period, two-treatment, crossover design to compare the pharmacokinetic (PK) characteristics and tolerability of two bazedoxifene tablets when administered to 50 healthy Korean male volunteers. Enrolled subjects were randomly allocated to 2 sequences of a single oral administration of a test drug and a reference drug, or vice versa with a 14-day washout period between the two doses. Serial blood samples were collected over 96 h for PK analysis. Plasma concentration of bazedoxifene was assayed using liquid chromatography-tandem spectrometry mass. Forty-five participants completed the study with no clinically relevant safety issues. The peak concentrations (Cmax, mean ± strandard deviation) of reference drug and test drug were 3.191 ± 1.080 and 3.231 ± 1.346 ng/mL, respectively, and the areas under the plasma concentration‐time curve from 0 to the last measurable concentration (AUClast) were 44.697 ± 21.168 ng∙h/mL and 45.902 ± 23.130 ng∙h/mL, respectively. The geometric mean ratios of test drug to reference drug and their 90% confidence intervals for Cmax and AUClast were 0.9913 (0.8828–1.1132) and 1.0106 (0.9345–1.0929), respectively. The incidence of adverse events between the two formulations was similar. The present study showed that PK and tolerability of two bazedoxifene tablet formulations were comparable when administered to healthy Korean male volunteers.

A Study of Evaluating Eye Movement Based on Ocular Motor Score for Children with Spastic Cerebral Palsy

Purpose@#The purpose of this study is to introduce a tool for evaluating eye movement and analyze the reliability of measurement based on 10 cases of evaluating the oculomotor function of children with spastic cerebral palsy @*Methods@#The participants were selected by 6 medical and welfare institutions in Busan as GMFCS grade 1-3 among spastic diplegia and hemiplegia. Seven examiners evaluated 3 children for the evaluation of inter-rater agreement of Ocular Motor Score (OMS) and evaluated the condition of the ocular motor of 10 children using OMS, a re-examination was performed at six weeks after the initial examination. SPSS ver.25.0 was used to calculate the interclass correlation coefficient and Wilcoxon’s signed-rank test, Mann Whitney-U test. @*Results@#The inter-rater agreement of OMS was 0.89. Second mean values were decreased compared first examination in motility/ductions/version, saccades and smooth pursuit, but there was no significant difference. Children under 6 years old had a high mean value of saccades in first examination and the motility/ductions/version, fixation, saccades in second examination, but there was no significant difference. Spastic diplegia children’s mean values were higher in head posture, fixation in 8 gaze directions than hemiplegia children in both first and second examination, but there were no significant differences. @*Conclusion@#Ocular motor function in 10 children of spastic children who participated in the study and could see that the scores was differed depending on age, type, grade of cerebral palsy. OMS may be available for this purpose.

A Study of Evaluating Eye Movement Based on Ocular Motor Score for Children with Spastic Cerebral Palsy

Purpose@#The purpose of this study is to introduce a tool for evaluating eye movement and analyze the reliability of measurement based on 10 cases of evaluating the oculomotor function of children with spastic cerebral palsy @*Methods@#The participants were selected by 6 medical and welfare institutions in Busan as GMFCS grade 1-3 among spastic diplegia and hemiplegia. Seven examiners evaluated 3 children for the evaluation of inter-rater agreement of Ocular Motor Score (OMS) and evaluated the condition of the ocular motor of 10 children using OMS, a re-examination was performed at six weeks after the initial examination. SPSS ver.25.0 was used to calculate the interclass correlation coefficient and Wilcoxon’s signed-rank test, Mann Whitney-U test. @*Results@#The inter-rater agreement of OMS was 0.89. Second mean values were decreased compared first examination in motility/ductions/version, saccades and smooth pursuit, but there was no significant difference. Children under 6 years old had a high mean value of saccades in first examination and the motility/ductions/version, fixation, saccades in second examination, but there was no significant difference. Spastic diplegia children’s mean values were higher in head posture, fixation in 8 gaze directions than hemiplegia children in both first and second examination, but there were no significant differences. @*Conclusion@#Ocular motor function in 10 children of spastic children who participated in the study and could see that the scores was differed depending on age, type, grade of cerebral palsy. OMS may be available for this purpose.

Proposal for improving the system of physical therapy education and the Korean physical therapist licensing examination based on a comparison of the systems in World Confederation for Physical Therapy member countries / 보건의료교육평가

No abstract available.

Suggestions for a standard clinical practice curriculum and learning objectives for physical therapy education in Korea / 보건의료교육평가

No abstract available.

Is there an agreement among the items of the Korean physical therapist licensing examination, learning objectives of class subjects, and physical therapists' job descriptions? / 보건의료교육평가

PURPOSE: To determine the agreement among the items of the Korean physical therapist licensing examination, learning objectives of class subjects, and physical therapists' job descriptions. METHODS: The main tasks of physical therapists were classified, and university courses related to the main tasks were also classified. Frequency analysis was used to determine the proportions of credits for the classified courses out of the total credits of major subjects, exam items related to the classified courses out of the total number of exam items, and universities that offer courses related to the Korean physical therapist licensing examination among the surveyed universities. RESULTS: The proportions of credits for clinical decision making and physical therapy diagnosis-related courses out of the total number credits for major subjects at universities were relatively low (2.06% and 2.58%, respectively). Although the main tasks of physical therapists are related to diagnosis and evaluation, the proportion of physiotherapy intervention-related items (35%) was higher than that of examination and evaluation-related items (25%) on the Korean physical therapist licensing examination. The percentages of universities that offer physical therapy diagnosis and clinical decision making-related courses were 58.62% and 68.97%, respectively. CONCLUSION: Both the proportion of physiotherapy diagnosis and evaluation-related items on the Korean physical therapist licensing examination, and the number of subjects related to clinical decision making and physical therapy diagnosis in the physical therapy curriculum, should be increased to ensure that the examination items and physical therapy curriculum reflect the practical tasks of physical therapists.

The Effects of Eupatilin (Stillen(R)) on Motility of Human Lower Gastrointestinal Tracts

Gastrointestinal motility consists of phasic slow-wave contractions and the migrating motor complex (MMC). Eupatilin (Stillen(R)) has been widely used to treat gastritis and peptic ulcers, and various cytokines and neuropeptides are thought to be involved, which can affect gastrointestinal motility. We performed a study to identify the effects of eupatilin on lower gastrointestinal motility with electromechanical recordings of smooth muscles in the human ileum and colon. Ileum and colon samples were obtained from patients undergoing bowel resection. The tissues were immediately stored in oxygenated Krebs-Ringer's bicarbonate solution, and conventional microelectrode recordings from muscle cells and tension recordings from muscle strips and ileal or colonic segments were performed. Eupatilin was perfused into the tissue chamber, and changes in membrane potentials and contractions were measured. Hyperpolarization of resting membrane potential (RMP) was observed after administration of eupatilin. The amplitude, AUC, and frequency of tension recordings from circular and longitudinal smooth muscle strips and bowel segments of the ileum and colon were significantly decreased after admission of eupatilin. Eupatilin elicited dose-dependent decreases during segmental tension recordings. In conclusion, eupatilin (Stillen(R)) showed inhibitory effects on the human ileum and colon. We propose that this drug may be useful for treating diseases that increase bowel motility, but further studies are necessary.

Augmenting Effect of DA-9601 on Ghrelin in an Acute Gastric Injury Model

BACKGROUND/AIMS: Acute gastric injury by alcohol or indomethacin has been reported to be prevented by DA-9601, an extract of the herb Artemisia asiatica. Ghrelin, an endogenously produced gastrointestinal peptide hormone, has also been demonstrated to play a role in gastric mucosal defense. The aim of this study was to investigate the effects of DA-9601 on ghrelin in an acute gastric injury model induced by alcohol or indomethacin. METHODS: A total of 140 Sprague-Dawley rats were divided into two groups, a placebo group and a DA-9601-pretreated group. Thirty minutes later, half of the rats in each group received ethanol injury and the other half received indomethacin injury. Levels of serum ghrelin and gastric mucosal ghrelin mRNA were measured by ELISA and RT-PCR, respectively. RESULTS: Immediately after ethanol administration, ghrelin increased in both groups pretreated with DA-9601 and placebo. However, the increase occurred more rapidly and was higher in the DA-9601-pretreated rats than in the controls that did not receive DA-9601-pretreatment. Similarly, from 30 minutes to 2 hours after indomethacin administration, the DA-9601-pretreated rats showed a significant increase in serum and gastric mucosal ghrelin concentrations, whereas placebo-pretreated rats showed only a mild increase. CONCLUSIONS: DA-9601 potentiates the endogenous production and secretion of ghrelin in acute gastric injury models induced by ethanol or indomethacin.

Suppressive Effects of Antioxidant DA-9601 on Hepatic Fibrosis in Rats / 대한간학회지

BACKGROUND/AIMS: Oxidative stress is one of the important underlying mechanisms of hepatic fibrosis. DA-9601, the ethanol extracts of Artemisia asiatica, has been reported to possess strong antioxidative and cytoprotective actions. We tried to evaluate whether antioxidant can ameliorate dimethylnitrosamine (DMN)-induced hepatic fibrosis. METHODS: Rat hepatic fibrosis was induced by intraperitoneal administrations of 10 mg DMN six times. Additionally, rats of one group were started daily with DA-9601 30 mg/kg containing diets and another group was fed a pellet diet containing DA-9601 100 mg/kg. The immunohistochemical studies for collagen, alpha-smooth muscle actin (alpha-SMA), and fibronectin, the measurements of hepatic malondialdehyde (MDA) and collagens, and the changes of liver function profiles were performed. Hepatic stellate cells (HSC) were isolated and in vitro effects of DA-9601 on HSC activations were measured. RESULTS: DA-9601 significantly attenuated the loss of body weights (p<0.05), the reduction of liver wet weights (p<0.05), and the elevation of liver enzymes provoked by DMN administrations. DMN injections caused the severe fibrosis of portal tract, hepatic inflammation, and significant oxidative damages, but DA-9601 treatment significantly reduced the mean scores of hepatic fibrosis, the amounts of hepatic collagens, and hepatic MDA levels. The prominent decreases in the expressions of collagens type I and III, alpha-SMA, and fibronectin or hepatic inflammations were observed in DA-9601-treated groups dose-dependently and similar efficacy was also proven in in vitro HSC experiment. CONCLUSIONS: DA-9601 effectively protected rat liver tissues against the DMN-induced hepatic fibrosis. Antioxidant could be considered as a supplementary therapeutic for alleviating the hepatic fibrosis.

Radiation-Induced Proctitis in Rat and Role of Nitric Oxide / 대한방사선종양학회지

PURPOSE: Proctitis is one of acute complications encountered when radiotherapy was applied to the pelvis. Radiation-induced proctitis represents similar microscopic findings that are observed in inflammatory bowel disease (IBD). Nitric oxide (NO) plays an important role in the inflammatory process and many data suggest a close relationship between NO production and gastrointestinal inflammation. This study was aimed to establish the optimal radiation dose for radiation-induced proctitis in rat and to find a relationship between radiation proctitis and NO production. MATERIALS AND METHODS: Female Wistar rats, weighing from 150 to 220 g, received various doses(10-30 Gy) of radiation to the rectum. On the 5th and 10th day after irradiation, rectal specimens were evaluated grossly and microscopically. In addition, the degree of NO production by irradiation dose was evaluated by study with NOS expression and nitrite production in the irradiated rectal tissue. To evaluate relationship between radiation proctitis and NO, we administered aminoguanidine, iNOS inhibitor and L-arginine, substrate of NOS to rats from 2 days before to 7 days after the irradiation. RESULTS: There were obvious gross and histological changes after 17.5 Gy or higher radiation dose but not with 15 Gy or less radiation dose. Twenty Gy or higher dose of radiation caused Grade 4 damage in most of rectal specimens which were more likely to be related to the late complications such as fibrosis, rectal bleeding and rectal obstruction. A single fraction of 17.5 Gy to the rat rectum is considered to be an optimal dose to produce commonly experienced proctitis in the clinic. The result demonstrated that severity of microscopic damage of rectal mucosa from irradiation significantly correlated with iNOS overexpression. However, administration of iNOS inhibitor or substrate of iNOS did not influence the degree of rectal damage. CONCLUSION: A single fraction of 17.5 Gy irradiation to the rat rectum considered to be an optimal dose for radiation induced proctitis model. These results indicated that an excess production of NO contributes to pathogenesis of radiation-induced proctitis in part but was not the direct cause of rectal damage.

A rat model for radiation-induced proctitis

Radiation proctitis is a frequent acute complication encountered with pelvic irradiation. This study was aimed at establishing the optimal radiation dose for radiation-induced proctitis in rats. Female Wistar rats were used. The rectal specimens were examined morphologically at 5th and 10th day following 10-30 Gy irradiation in single fraction. With increasing dose, mucosal damage became worse, and there was a prominent reaction after > or =15 Gy. We selected 17.5 Gy as an optimal dose for radiation proctitis and examined specimens at day 1-14 and at week 4, 6, 8, and 12 after 17.5 Gy. The rectal mucosa revealed characteristic histological changes with time. An edema in lamina propria started as early as 1-2 days after irradiation and progressed into acute inflammation. On day 7 and 8, regeneration was observed with or without ulcer. Four weeks later, all regeneration processes have been completed with end result of either fibrosis or normal appearing mucosa. This study showed that the radiation injury of the rectum in rat develops in dose-dependent manner as it has reported in previous studies and suggested that 17.5 Gy in single fraction is the optimum dose to evaluate the protective effect of various medications for radiation proctitis in face of the clinical situation.