Comparison of the acid suppression effects between low-dose esomeprazole and famotidine in healthy subjects.

OBJECTIVE: Famotidine, an H2 receptor antagonist (H2RA), is mainly prescribed to alleviate the early symptoms of gastritis. Our aim was to explore the possibilities of low-dose esomeprazole as a treatment of gastritis as well as the pharmacodynamic (PD) properties of esomeprazole and famotidine. MATERIALS AND METHODS: A randomized, multiple-dose, 6-sequence, 3-period crossover study was conducted with a 7-day washout between periods. For each period, the subjects were administered one dose of esomeprazole 10 mg or famotidine 20 mg or esomeprazole 20 mg each day. To evaluate the PDs, the 24-hour gastric pH was recorded after single and multiple doses. The mean percentage of time during which the gastric pH was above 4 was evaluated for PD assessment. To confirm the pharmacokinetic (PK) characteristics of esomeprazole, blood was collected for up to 24 hours after multiple doses. RESULTS: 26 subjects completed the study. Following the multiple doses of esomeprazole 10 mg, esomeprazole 20 mg, and famotidine 20 mg, the mean percentages of time during which the gastric pH was above 4 over the course of 24 hour were 35.77 ± 19.56%, 53.75 ± 20.55%, and 24.48 ± 17.36%, respectively. After multiple doses, the time of peak plasma concentration at steady state (tmax,ss) was 1.00 and 1.25 hours for 10 and 20 mg of esomeprazole, respectively. The geometric mean ratio and its 90% confidence interval of area under the plasma drug concentration-time curve in steady state (AUCT,ss) and maximum concentration of drug in plasma in steady state (Cmax,ss) for esomeprazole 10 mg compared to 20 mg were 0.3654 (0.3381 - 0.3948) and 0.5066 (0.4601 - 0.5579), respectively. CONCLUSION: The PD parameters of esomeprazole 10 mg were comparable to those of famotidine after multiple doses. These findings provide support for further evaluating the use of 10 mg of esomeprazole as a treatment option for gastritis.

Pharmacokinetic comparison between tablet of varenicline tartrate and orally disintegrating film of varenicline salicylate in healthy subjects.

OBJECTIVE: Varenicline is an efficacious aid for smoking cessation. In this study, the pharmacokinetics and safety were compared between film-coated tablets of varenicline tartrate (reference drug) and the newly developed orally disintegrating films of varenicline salicylate (test drug), both of them contained 1 mg of varenicline. MATERIALS AND METHODS: A randomized, open-label, single-dose, two-sequence, two-period crossover study was conducted in healthy male subjects. Serial blood samples were obtained for up to 72 hours in each period, with a washout period of 7 days or more. The pharmacokinetic parameters were calculated using the noncompartmental method. Safety profiles were assessed throughout the study. RESULTS: A total of 28 subjects completed the study. The plasma varenicline concentration-time profiles were similar for the two study drugs. The maximum plasma varenicline concentration (Cmax) was 5,768.95 ng/L (mean) and 5,780.55 ng/L for the test drug and reference drug, respectively. The areas under the concentration-time curve from time 0 to the last measurable time point (AUC0-t) were 94,086.30 h×ng/L and 89,958.55 h×ng/L for the test drug and reference drug, respectively. The geometric mean ratios (90% confidence intervals) of the test drug to the reference drug for Cmax and AUC0-t were 0.9955 (0.9488 - 1.0444) and 1.0449 (0.9848 - 1.1088), respectively, which fell within the bioequivalence range of 0.8 - 1.25. There was no difference in safety between the study drugs. CONCLUSION: The pharmacokinetics and safety profiles were similar between the two study drugs. The orally disintegrating film of varenicline salicylate can be an alternative to varenicline tartrate tablets.

A meaning-centered spiritual care training program for hospice palliative care teams in South Korea: development and preliminary evaluation.

BACKGROUND: Spirituality is a fundamental, intrinsic aspect of human beings and should be a core component of quality palliative care. There is an urgent need to train hospice palliative care teams (HPCTs) to enhance their ability to provide spiritual care. This study aimed to develop and evaluate a meaning-centered, spiritual care training program (McSCTP) for HPCTs (McSCTP-HPCTs). METHODS: The modules' content was informed by Viktor Frankl's meaning-centered logotherapy with its emphasis on spiritual resources, as well as the spiritual care model of the Interprofessional Spiritual Care Education Curriculum (ISPEC). Following development, we conducted a pilot test with four nurses. We used the results to inform the final program, which we tested in an intervention involving 13 members of HPCTs. We took measurements using self-administered questionnaires at three points before and after the intervention. Using descriptive statistics, the Mann-Whitney U test, and the Kruskal-Wallis test, we analyzed the participants' demographic and career-related characteristics, as well as the degree of variance between three outcome variables: compassion fatigue (CF), spiritual care competencies (SCCs), and spiritual care therapeutics (SCT). RESULTS: We divided the McSCTP-HPCTs into five modules. Module I: The HPCTs' SCC evaluation, understanding the major concepts of spiritual care and logotherapy; Modules II-IV: Meaning-centered interventions (MCIs) related to spiritual needs (existential, relational, and transcendental/religious); Module V: The process of meaning-centered spiritual care. The preliminary evaluation revealed significant differences in all three outcome variables at the posttest point (CF, p = 0.037; SCCs, p = 0.005; SCT, p = 0.002). At the four-week follow-up test point, we only found statistical significance with the SCCs (p = 0.006). CONCLUSIONS: The McSCTP-HPCTs is suitable for use in clinical settings and provides evidence for assessing the SCCs of HPCTs.

Comparison of the pharmacokinetic characteristics and bioequivalence between two nanosuspension formulations of megestrol acetate in healthy Korean male subjects.

Megestrol is commonly used to address appetite loss, cachexia, and significant weight loss in cancer or acquired immune deficiency syndrome patients. This study aimed to assess the pharmacokinetics and determine the bioequivalence of two orally administered megestrol acetate suspensions (625 mg/5 mL) in healthy Korean male subjects. A randomized, open-label, single-dose crossover study was conducted involving fifty-four healthy male subjects who were randomized into two sequence groups. Each subject received either a test or reference drug formulation of 625 mg/5 mL megestrol acetate with a two-week washout period between treatments. Plasma samples were collected before and up to 120 hours after administration, and their plasma drug concentrations were analyzed using validated liquid chromatography-mass spectrometry/mass spectrometry. The pharmacokinetic parameters were calculated, and bioequivalence was confirmed if the 90% confidence intervals of the geometric mean ratios were within the specified bounds of 80.00% to 125.00%. In total, fifty-two subjects completed the study, contributing to the pharmacokinetic analysis. The 90% confidence intervals for the geometric mean ratios of the test formulation compared to the reference formulation were 93.85% to 108.90% for maximum plasma concentration and 91.60% to 101.78% for area under the concentration-time curve from the point of administration to last time point of blood sampling. Throughout the study, no serious or unexpected adverse events were observed. The pharmacokinetic profiles of both formulations of megestrol acetate (625 mg) were comparable and well tolerated in healthy Korean male adult subjects. The test formulation met regulatory criteria for bioequivalence. Trial Registration: ClinicalTrials.gov Identifier: NCT06147908.

Pharmacokinetic and Pharmacodynamic Characteristics of Pelubiprofen Tromethamine vs. Pelubiprofen in Healthy Subjects.

Compared to pelubiprofen, a cyclooxygenase-2-selective inhibitor, pelubiprofen tromethamine has been reported to exhibit improved solubility and absorption. Pelubiprofen tromethamine combines the anti-inflammatory effect of pelubiprofen with the gastric protective function of tromethamine salt, making it a relatively safe class of non-steroidal anti-inflammatory drugs with low levels of gastrointestinal side effects in addition to its original analgesic, anti-inflammatory, and antipyretic effects. This study assessed the pharmacokinetic and pharmacodynamic characteristics of pelubiprofen and pelubiprofen tromethamine in healthy subjects. Two independent clinical trials were performed in healthy subjects using a randomized, open-label, oral, single-dose, two-sequence, four-period, crossover design. In Study I and Study II, subjects received 25 mg of pelubiprofen tromethamine and 30 mg of pelubiprofen tromethamine, respectively, with 30 mg of pelubiprofen being the reference. Study I fell within the bioequivalence study criteria. A trend of increased absorption and exposure for 30 mg of pelubiprofen tromethamine vs. the reference in Study II was observed. The maximum cyclooxygenase-2 inhibitory effect of 25 mg of pelubiprofen tromethamine was approximately 98% compared to the reference, showing no significant pharmacodynamic variation. It is thus predicted that 25 mg of pelubiprofen tromethamine would show no clinically significant discrepancies in clinical analgesic and antipyretic effects from 30 mg of pelubiprofen.

Influence of Renal Function on the Single-Dose Pharmacokinetics of Besifovir, a Novel Antiviral Agent for theTreatment of Hepatitis B Virus Infection.

Per the well-known resistance of hepatitis B virus to nucleoside/nucleotide analogs, alternative treatment options with higher resistance barriers have been approved for use in both treatment-naïve and lamivudine-resistant hepatitis B virus infections. This phase I study was conducted in adults with normal and impaired renal function to evaluate the effect of renal impairment on the pharmacokinetics of besifovir, a prodrug of an acyclic nucleotide phosphonate, that is mainly cleared via renal excretion. An open-label, single-dose parallel-group clinical study was conducted in subjects with normal renal function and mild, moderate, and severe renal impairment. Subjects received a single oral dose of besifovir dipivoxil 150 mg, and serial blood and urine samples were collected for up to 72 hours after dosing to assess the pharmacokinetic characteristics of besifovir. The extent of plasma exposure of besifovir, detected as its major and active metabolites, LB80331 and LB80317, respectively, increased with worsening renal function. Compared to the subjects with normal renal function, the mean areas under the concentration-time curves of LB80331 increased by 1.5-, 2.5-, and 4.5-fold in subjects with mild, moderate, and severe impairment, respectively. LB80317 showed a 1.8-, 3.2-, and 6.2-fold increase in subjects with mild, moderate, and severe renal impairment compared to those with normal function. The ratios of LB80331 renal clearance and the average estimated glomerular filtration rate of each renal impairment group with respect to the normal group were similar. The increase in plasma exposure and decrease in renal clearance suggest the need to adjust dosage regimens in patients with moderate to severe renal impairment.

Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen.

OBJECTIVE: Prostaglandin E2 (PGE2) synthesis is modulated by COX2. Changes in PGE2 could be used to quantify the COX2 inhibition after ibuprofen administration. This study investigated the pharmacokinetic and pharmacodynamic relationships for COX2 inhibition according to three formulations of ibuprofen in healthy male subjects. MATERIALS AND METHODS: A randomized, open-label, single-dose, three-treatment, six-sequence crossover study was performed in 36 healthy South Korean male volunteers. Enrolled subjects received the following three 200 mg ibuprofen formulations: ibuprofen arginine, solubilized ibuprofen capsule, and standard ibuprofen. Pharmacokinetic and pharmacodynamic blood samples were collected for 16 hours following treatment. For pharmacodynamic evaluations, lipopolysaccharide (LPS)-induced PGE2 inhibition at each time point compared to predose was measured. Noncompartmental analysis was used for pharmacokinetic assessment, and time-weighted average inhibition (WAI) of PGE2 was applied to the pharmacodynamic evaluation. RESULTS: After a single oral dose of the ibuprofen formulations, the median times to maximum concentration were 0.42, 0.5, and 1.25 hours in ibuprofen arginine, solubilized ibuprofen capsule, and ibuprofen, respectively. The maximum observed plasma concentration was lower in ibuprofen, and the area under the plasma concentration-time curve was comparable among the three formulations. A significant difference was observed between fast-acting formulations and standard ibuprofen tablets for both maximum concentration and time taken to reach it. Individual formulations had an effect on PGE2 WAI during the 8 hours following treatment, resulting in significantly lower WAI in standard ibuprofen: ibuprofen arginine 18.4%, solubilized ibuprofen capsule 18.4%, and standard ibuprofen 11.6%. CONCLUSION: Rapid absorption and higher peak concentration were observed in ibuprofen arginine and the solubilized ibuprofen capsule. Additionally, fast-acting formulations had more predominant inhibitory activity on the COX2 enzyme.

Associations between estimated desaturase activity and insulin resistance in korean boys.

OBJECTIVES: Obesity in childhood increases the risk of obesity in adulthood, and is predictive of the development of metabolic disorders. The fatty acid compositions of various tissues, including blood, are associated with obesity and obesity-associated disorders. Thus, tracking plasma phospholipid (PL) features and metabolic parameters in young individuals may strengthen the utility of fatty acid composition as an early biomarker of future metabolic disorders. METHODS: Anthropometric and blood biochemical data were obtained from 131 Korean males aged 10.5 ± 0.4 years, and followed up at 2 years. We analyzed the plasma PL fatty acids according to obesity. Obese children were defined as those with a body mass index (BMI) greater than the 85(th) percentile for age and gender, based on Korean child growth standards. RESULTS: Activities of lipid desaturases, stearyl-CoAD (SCD-16,16:1n-7/16:0), delta-6D (D6D, 20:3n-6/18:2n-6), and delta-5D (D5D, 20:4n-6/20:3n-6), were estimated. Obese individuals had significantly higher proportions of palmitoleic acid (16:1n-7) and dihomo-gamma linolenic acid (DGLA, 20:3n-6) at both baseline and follow-up than did lean individuals. The activities of SCD-16 and D6D were higher in obese than lean boys. The baseline SCD-16 activity level was positively associated with the baseline waist circumference (WC) and the metabolic risk score. The baseline D6D level was positively associated with WC and also with the homeostasis model of assessment of insulin resistance (HOMA-IR), a surrogate marker of insulin resistance (IR), and metabolic risk score at both baseline and follow-up. CONCLUSION: In young Korean males, higher D6D activity predicts the future development of IR and associated metabolic disorders including dyslipidemia.

Physicochemical Characteristics and Antioxidant Capacity of Rice Cake (Sulgitteok) Supplemented with Lyophilized Sedum sarmentosum (Dolnamul) Powder.

This study was performed to increase the availability of Sedum sarmentosum (Dolnamul) and to improve the nutraceutical value of rice cakes (sulgitteok). The contents of crude protein, mineral, dietary fiber, water holding capacity, and hardness significantly and directly increased with lyophilized sedum powder (SP). Pore ratio and expansion rate decreased in samples containing more than 10% SP compared to the control. In a sensory evaluation, a positive correlation was detected between overall acceptability and taste (R (2)=0.99, p<0.01), and color (R (2)=0.72, p<0.05). Total polyphenol contents of the SP-treated groups were significantly elevated, accompanied by an increase in radical scavenging ability estimated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Replacing 10% of the rice powder with SP efficiently improved the antioxidant and nutritional values of sulgitteok as well as its the sensory quality.

Development of the standard hospice and palliative care education program in Korea: results from the demonstration project.

PURPOSE: To describe development of the Standard Hospice & Palliative Care Education Program in Korea, a basic training program for hospice & palliative care professionals, and to report preliminary results from the 2008-2009 demonstration project at 2 sites that support its effectiveness. METHOD: We developed the Standard Hospice & Palliative Care Education Program, consisting of 19 modules, under the initiative and financial support of the Ministry of Health, Welfare, and Family Affairs. We adapted the train-the-trainer model and benchmarked the EPEC (Education in Palliative and End-of-life Care) course. In order to evaluate the effectiveness of the program, session evaluation, pre-post test of knowledge, and overall course evaluation were assessed by participants. RESULTS: The demonstration program included a total of 105 participants. Overall rating by participants was 4.1 for relevance and usefulness of program contents (range, 4.1-4.2; 1 = strongly disagree, 5 = strongly agree) and 4.1 for the trainer's teaching skills (range, 4.0-4.2). Participants demonstrated significant improvement in their knowledge on the pre-post test for 6 of the 17 modules, and reported that they had gained confidence in their ability to perform palliative care practices (overall mean ratings, 4.0, range; 3.6-4.3; 1 = very low, 5 = very high). Overall evaluation of the program was very high (very satisfied or satisfied; 86%). CONCLUSION: Development of the Standard Hospice & Palliative Care Education Program was successful, and its preliminary effectiveness was shown by the demonstration program. Comments on our experience in Korea would be helpful to efforts in other countries, particularly those with limited resources for hospice and palliative care.