Association of pre-operative medication use with post-surgery mortality and morbidity in oncology patients receiving comprehensive geriatric assessment.

BACKGROUND: Comprehensive geriatric assessment (CGA) has become a predictor for elderly cancer patients in post-surgical complications, including post-discharge institutionalization and mortality. AIMS: To determine whether pre-operative medication use is associated with post-operative morbidity and mortality in oncology patients receiving CGA. METHODS: Patients aged 65 years or older who were scheduled for cancer surgery and presented for CGA were included in the present study. Baseline characteristics of patients were collected from electrical medical records, and pre-operative medication review was performed. The primary outcome was death within 30 days after surgery and post-discharge institutionalization. RESULTS: A total of 475 cancer patients were included. Among them, three patients died within 30 days after surgery and 14 patients were discharged to another institution. All patients who died within 30 days after surgery had polypharmacy with marginal significance (P = 0.087). Multivariate analysis models were constructed using significant factors for post-surgery institutionalization from univariate analysis: Model I (polypharmacy and transfusion), Model II (polypharmacy and infection), and Model III (polypharmacy, transfusion, and infection). Infection was the most significant factor. Its adjusted odds ratio was as large as 11.1 and attributable risk was almost 91%. In pre-surgery medication use, only polypharmacy showed significant association with post-discharge institutionalization. Attributable risk of polypharmacy was around 75%. CONCLUSIONS: It is possible that pre-operative medication use has impact on death and post-discharge institutionalization in geriatric oncology patients, further highlighting the importance of medication optimization for elderly patients with cancer surgery.

Association of pre-operative medication use with post-operative delirium in surgical oncology patients receiving comprehensive geriatric assessment.

BACKGROUND: Older patients undergoing surgery tend to have a higher frequency of delirium. Delirium is strongly associated with poor surgical outcomes. This study evaluated the association between pre-operative medication use and post-operative delirium (POD) in surgical oncology patients receiving comprehensive geriatric assessment (CGA). METHODS: A total of 475 patients who were scheduled for cancer surgery and received CGA from January 2014 to June 2015 were included. Pre-operative medication review through CGA was conducted on polypharmacy (≥5 medications), delirium-inducing medications (DIMs), fall-inducing medications (FIMs), and potentially inappropriate medications (PIMs). POD was confirmed by psychiatric consultation, and DSM-V criteria were used for diagnosing delirium. The model fit of the prediction model was assessed by computing the Hosmer-Lemeshow goodness-of-fit test. Effect size was measured using the Nagelkerke R(2). Discrimination of the model was assessed by an analysis of the area under receiver operating curve (AUROC). RESULTS: Two models were constructed for multivariate analysis based on univariate analysis; model I included dementia and DIM in addition to age and sex, and model II included PIM instead of DIM of model I. Every one year increase of age increased the risk of POD by about 1.1-fold. DIM was a significant factor for POD after adjusting for confounders (AOR 12.78, 95 % CI 2.83-57.74). PIM was also a significant factor for POD (AOR 5.53, 95 % CI 2.03-15.05). The Hosmer-Lemeshow test results revealed good fits for both models (χ(2) = 3.842, p = 0.871 for model I and χ(2) = 8.130, p = 0.421 for model II). The Nagelkerke R(2) effect size and AUROC for model I was 0.215 and 0.833, respectively. Model II had the Nagelkerke R(2)effect size of 0.174 and AUROC of 0.819. CONCLUSIONS: These results suggest that pharmacists' comprehensive review for pre-operative medication use is critical for the post-operative outcomes like delirium in older patients.

Awareness of the adverse effects associated with prophylactic corticosteroid use during docetaxel therapy.

PURPOSE: Weekly or tri-weekly docetaxel treatment mandates the use of dexamethasone to prevent toxicity. However, the adverse effects of prophylactic steroid use are often overlooked. We investigated the incidence of corticosteroid-associated adverse effects during docetaxel therapy, focusing on hyperglycemia and infection as well as the identification of possible risk factors. METHODS: This study was conducted through retrospective chart review of 632 patients who started docetaxel-based chemotherapy between July 2011 and June 2012 at Seoul National University Hospital. Hyperglycemia was defined as more than two random glucose levels >200 mg/dL. All documented episodes of infection that required treatment with antibiotics were regarded as infectious episodes. RESULTS: The incidences of hyperglycemia in overall patients and in patients without previous diabetes mellitus were 13.7 and 10.9%, respectively. Infectious episodes greater than grade 2 and grade 3 developed in 29.6 and 19.9% of patients, respectively. Multivariable logistic regression analysis showed that body mass index and previous diabetes mellitus were independent risk factors for hyperglycemia, whereas corticosteroid dose was not. Treatment duration and frequency of high blood glucose levels over 200 mg/dL were independent risk factors for infection. CONCLUSIONS: Due to the significant difference in patient and treatment characteristics, we could not obtain meaningful comparisons between weekly and tri-weekly docetaxel administration regimens. This study suggests that adverse effects associated with prophylactic steroid use need to be recognized and optimally managed during docetaxel therapy.

Low adherence to upfront and extended adjuvant letrozole therapy among early breast cancer patients in a clinical practice setting.

OBJECTIVE: The aim of this study was to investigate the prevalence and causes of early discontinuation and non-adherence to upfront and extended adjuvant letrozole therapy in breast cancer patients. METHODS: Adherence was assessed using medical charts and longitudinal pharmacy records of 609 patients who initiated adjuvant letrozole between January 2002 and April 2011. A Cox proportional hazards regression model was adopted to identify potential predictors of non-adherence. RESULTS: The overall adherence rate after 1 year of therapy was 79.5%, with cumulative rates declining to 63.7% after 3 years and 57.1% after 5 years. A significantly lower rate of adherence in the extended adjuvant group was observed compared with the upfront adjuvant group (49.0 vs. 72.5%, p < 0.001). Adverse events (50.4%) were the major cause of early discontinuation, with musculoskeletal pain (73.2%) being the single most cited reason. Additional factors correlating with non-adherence in the upfront adjuvant group included a delay in initiation of adjuvant hormone therapy, breast-conserving surgery, calcium supplements, bisphosphonate therapy and concomitant medication for co-morbidity. CONCLUSIONS: We observed that approximately 57% of patients fully adhered to letrozole therapy over a 5-year treatment period, and that the adherence to extended letrozole was meaningfully lower than the upfront adjuvant letrozole in a clinical practice setting.

Signal detection of methylphenidate by comparing a spontaneous reporting database with a claims database.

Data mining is critical for signal detection in pharmacovigilance systems. In this study, we compared signals between spontaneous reporting data and health insurance claims data for a socially issued drug, methylphenidate. We implemented data-mining tools for signal detection in both databases: Reporting Odds Ratios (ROR), Proportional Reporting Ratios (PRR), Chi-squared test, and Information Component (IC), in addition to a Relative Risk (RR) tool in the claims database. The claims database generated 15, 15, 36, 1, and 1 adverse drug reactions (ADRs) by ROR, PRR, chi-square, IC, and RR, respectively. The World Health Organization (WHO) spontaneous database generated 91, 91, 137, and 96 ADRs by ROR, PRR, chi-square, and IC, respectively. We found seven potential matching associations from the claims and WHO databases, but only one of them was present in the Korean spontaneous reporting database. In Korea, spontaneous reporting is still underreported and there is a small amount of data for Koreans. Signal comparison between the claims and WHO databases can provide additional regulatory insight.

Association between preoperative use of antithrombotic medications and intraoperative transfusion in older patients undergoing cancer surgery.

BACKGROUND: Management of antiplatelet agents and other chronic anticoagulation medications in patients scheduled for surgery can reduce intraoperative bleeding complications. However, few studies on the association of antithrombotics, relative to their duration of action, with intraoperative transfusion have been conducted. We aimed to determine the association of recent use of antithrombotics, relative to their duration of action, with intraoperative transfusion in elderly people undergoing cancer surgery. METHODS: The study subjects were patients aged 65 years or older who were scheduled for cancer surgery and presented for comprehensive geriatric assessment. We reviewed the baseline patient characteristics obtained from electronic medical records and the patients' preoperative medication history, including anticoagulants, antiplatelet agents, and streptokinase/streptodornase. RESULTS: A total of 475 cancer patients were included. Multivariate analysis showed that long-acting anticoagulant therapy before surgery was a significant risk factor for intraoperative transfusion. Long-acting anticoagulants increased the risk of transfusion approximately 15.9-fold (95% CI 1.9-136.2). The attributable risk of long-acting anticoagulants to transfusion was approximately 93.7%. Also, low body mass index (BMI) and hepato-pancreato-biliary (HPB) surgery were significantly associated with intraoperative transfusion. The adjusted odds ratios for low BMI (<18.5 kg/m2) and HPB surgery (reference: lower gastrointestinal surgery) were 5.3 (95% CI 1.8-15.4) and 4.9 (95% CI 1.9-12.5), respectively. CONCLUSIONS: It was found that the perioperative use of long-acting anticoagulants was associated with an increased risk of intraoperative transfusion, further highlighting the importance of medication optimization for elderly patients with cancer surgery.

Association of pre-operative medication use with unplanned 30-day hospital readmission after surgery in oncology patients receiving comprehensive geriatric assessment.

BACKGROUND: This study aimed to determine whether pre-operative medication use is associated with unplanned 30-day readmission in elderly people undergoing cancer surgery. METHODS: Patients aged 65 years or older who were scheduled for cancer surgery and presented for comprehensive geriatric assessment were included. Comparisons of variables between patients with readmission and those without readmission were performed by univariate and multivariate analyses. RESULTS: A total of 473 patients were included. Multivariate analysis showed that pre-operative discontinuation-requiring medications (PDRMs) and gastrointestinal/hepato-pancreato-biliary (GI/HPB) cancer were significant factors for 30-day readmission. PDRM increased the risk of readmission by about 2.2-fold. Attributable risk of PDRM to readmission was around 55%. The adjusted odds ratio and attributable risk for GI/HPB surgery was 3.4 (95% CI 1.0-11.5) and 70.8%, respectively. CONCLUSIONS: Medication use has an impact on unplanned 30-day readmission in geriatric oncology patients, further highlighting the importance of medication optimization for elderly patients with cancer surgery.

Effects of scoparone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells.

The effects of scoparone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. PC12 cells treated with scoparone at concentrations of 100-200 microM showed a 128-136% increase in dopamine levels over the course of 24 hr. Scoparone significantly increased the secretion of dopamine into the culture medium. Under the same conditions, the activities of tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) were enhanced by treatment with 200 microM scoparone for 6-48 hr, but the activity of TH was regulated for a longer period than that of AADC. The intracellular levels of cyclic AMP and Ca(2+) were increased by treatment with 200 microM scoparone. The levels of TH mRNA and the phosphorylation of cyclic AMP-response element-binding protein (CREB) were also significantly increased by treatment with 200 microM scoparone. In addition, scoparone at a concentration of 200 microM stimulated the activities of cyclic AMP-dependent protein kinase (PKA), protein kinase C (PKC), and Ca(2+)/calmodulin kinase II (CaMK II). Finally, pretreatment with 200 microM scoparone reduced the cytotoxicity induced by L-DOPA (20-100 microM) at 24 hr. These results suggest that scoparone enhances dopamine biosynthesis by regulating TH activity and TH gene expression, which is mediated by the PKA, CREB, PKC, and CaMK II pathways, and protects cells from L-DOPA-induced cytotoxicity by inducing cyclic AMP-PKA systems in PC12 cells.

Formulation and evaluation of ubidecarenone transdermal delivery systems.

PURPOSE: This study is aimed to examine the feasibility of developing ubidecarenone (coenzyme Q(10), CoQ(10)) transdermal delivery systems (TDS). METHOD: In vitro permeation study using solution formulation and pressure-sensitive adhesive (PSA) TDS and in vivo pharmacokinetic study were conducted. RESULTS: When using solution formulations, isopropyl alcohol (103.39 +/- 1.61), ethyl alcohol (81.55 +/- 7.27), and the mixture of diethylene glycol monoethyl ether (DGME)/propylene glycol monolaurate (PGML) at the ratio of 60:40 (91.08 +/- 26.07) showed high flux (microg/cm(2)/hour). The addition of fatty acids to DGME-PGML failed to show profound enhancing effects; only unsaturated fatty acids such as linoleic acid and oleic acid at 3% and caprylic acid at 3% and 10% slightly increased permeation flux. CoQ(10) from the acrylic PSA TDS showed biphasic permeation profile that was permeated very rapidly up to the first 12 hours, and after that, permeation rate became slower. Overall, 6% fatty acids showed high permeation rates and the highest maximum flux of 9.3 microg/cm(2)/hour was obtained with a formulation containing 6% lauric acid in DGME-PGML (60:40). The in vivo pharmacokinetic study using TDS with 6% fatty acids in DGME-PGML (60:40) showed that the absorption of CoQ(10) decreased in the following order: TDS containing linoleic acid > oral dosage form > TDS with oleic acid > TDS with lauric acid > TDS with caprylic acid > TDS with capric acid. TDS containing oleic acid showed preferable pharmacokinetic profile with respect to lower C(max), comparable AUC, and prolonged t(1/2) and T(max) compared to oral administration of drug. CONCLUSIONS: For effective transdermal delivery system of CoQ(10), 6% linoleic acid or oleic acid in DGME-PGML (60:40) could be employed.

Preoperative medication use and its association with postoperative length of hospital stay in surgical oncology patients receiving comprehensive geriatric assessment.

AIM: The present study aimed to investigate whether preoperative medication use is associated with postoperative length of hospital stay in older adults undergoing cancer surgery. METHODS: Patients aged ≥65 years who were scheduled for cancer surgery and presented for preoperative comprehensive geriatric assessment were included in the present study. Cognitive function evaluation and preoperative medication review were carried out, as well as baseline characteristics of participants collected from electronic medical records. The primary efficacy variable was the postoperative length of stay (LOS) in hospital. RESULTS: A total of 475 cancer patients were included for the analysis. Baseline characteristics of participants including older age, lower body mass index (BMI) and male sex were associated with longer postoperative stay. Among the clinical variables, cancer type, number of medications, potentially inappropriate medication (PIM) and delirium-inducing medication were found as statistically significant factors for postoperative LOS. In multivariate analysis, variables independently associated with postoperative LOS were cancer type, PIM use, BMI, and the number of medications after controlling for age, BMI, sex, cancer type, the number of medications, PIM, and delirium-inducing medication. In subgroup analysis of gastrointestinal cancer, multiple linear regression analysis showed that PIM use and BMI were significantly associated with LOS after adjustment for age, sex, and number of medication. CONCLUSIONS: The present study supports the impact of medication use on postoperative LOS in geriatric oncology patients. The results add a further aspect to medication optimization in older patients undergoing cancer surgery. Geriatr Gerontol Int 2018; 18: 12-19.

Attitudes to proposed assessment of pharmacy skills in Korean pharmacist licensure examination.

PURPOSE: The survey aimed to obtain opinions about a proposed implementation of pharmacy skills assessment in Korean pharmacist licensure examination (KPLE). METHODS: A 16-question survey was distributed electronically to 2,738 people including 570 pharmacy professors of 35 pharmacy schools, 550 preceptors from 865 practice sites and 1,618 students who graduated in 2015. The survey solicited responses concerning the adequacy of the current KPLE in assessing pharmacy knowledge/skills/attitudes, deficiencies of pharmacy skills testing in assessing the professional competencies necessary for pharmacists, plans for pharmacy skills tests in the current KPLE, and subject areas of pharmacy practice. RESULTS: A total of 466 surveys were returned. The current exam is not adequate for assessing skills and attitudes according to 42%-48% of respondents. Sixty percent felt that skills test is necessary to assess qualifications and professional competencies. Almost two-thirds of participants stated that testing should be implemented within 5 years. More than 60% agreed that candidates should be graduates and that written and skills test scores can be combined for pass-fail decisions. About 70% of respondents felt that the test should be less than 2 hours in duration. Over half of the respondents thought that the assessor should be a pharmacy faculty member with at least 5 years of clinical experience. Up to 70% stated that activities related to patient care were appropriate and practical for the scope of skills test. CONCLUSION: Pharmacy skills assessment was supported by the majority of respondents.

Effects of inflammatory cytokine gene polymorphisms on warfarin maintenance doses in Korean patients with mechanical cardiac valves.

Cytokines that are involved in inflammation are related to blood coagulation, which could indirectly affect warfarin dose requirements. This study aimed to examine the effects of inflammatory cytokine gene polymorphisms on warfarin dose requirements for Korean patients with mechanical heart valves. In total, 191 patients with mechanical heart valves who were on warfarin anticoagulation therapy and maintained INR levels of 2-3 for three consecutive occasions were retrospectively followed up. In addition to vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 (CYP) 2C9 polymorphisms, the interferon-γ, interleukin-1ß (IL1B), interleukin-6, interleukin-10, transforming growth factor-ß1 (TGFB1), tumor necrosis factor-α, and C-reactive protein genotypes were determined. The predictive contribution of age, VKORC1, and CYP2C9 to variability was 46.0 %. The addition of IL1B and TGFB1 polymorphisms increased the R (2) to 48.8 % for stable dose requirements, and significantly higher doses were found, especially when the TGFB1 CC genotype was combined with the IL1B TT genotype. Based on the results, it was concluded that inflammatory cytokine genes, such as TGFB1 and IL1B, can be predictive variables for stable warfarin doses in Korean patients.

Development of clinical pharmacy services for intensive care units in Korea.

OBJECTIVE: To be utilized for the development of pharmacists' intervention service by determining factors which affect pharmacists' prescription interventions. SETTING: Patients who were admitted to intensive care units (ICUs) in internal medicine departments in Korea. METHODS: Data including age, gender, clinical departments, length of hospital stay, status of organ dysfunction, intervention status, frequently intervened drugs, and health care providers' questions were prospectively collected in ICUs in the department of internal medicine in a tertiary teaching hospital from January to December, 2012. MAIN OUTCOME MEASURE: Primary outcome was factors which affect pharmacists' prescription interventions. Secondary outcomes included frequencies of the intervention, intervention acceptance rates, intervention issues, and frequently intervened drugs. RESULTS: A total of 1,213 prescription interventions were made for 445 patients (33.1%) of the 1,344 patients that were analyzed. Length of hospital stay was significantly longer for the group that needed pharmacists' interventions (p < 0.001). Pharmacists' intervention requirements were significantly higher in patients with kidney dysfunction (p < 0.001). The percentage of intervention accepted was 96.8%, and interventions that were common were as follows (in order): clinical pharmacokinetic service, dosage or dosing interval changes, dosing time changes or dose changes, and total parenteral nutrition consultation. The five medications with the highest intervened frequency were (in order) vancomycin, famotidine, ranitidine, meropenem, and theophylline. CONCLUSION: The need for pharmacists' prescription interventions was highest among patients with longer length of stay and patients with kidney dysfunction. Based on these findings, prescription intervention activities could be initiated with severely ill patients. The results could be utilized in countries which are planning to develop pharmacists' intervention service.

Impact of immunosuppressant therapy on early recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND/AIMS: The most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated. METHODS: Ninety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 ± 1.3 ng/mL (mean ± SD). RESULTS: The 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive (18)fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05). CONCLUSIONS: Induction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients.

A cross-sectional study of factors related to gastrointestinal drug use in Korean adolescents.

Adolescence is critical in the habituation of diverse lifestyles and is a base for future physical well-being. Although gastrointestinal disorders are frequently reported in adolescents, studies related to GI drug use or related factors in Korean adolescents are rare. Thus, this study examined Korean adolescents for the use of GI drugs for abdominal symptoms and analyzed the associated factors. This cross-sectional study was done with a total of 2,416 students who completed a given questionnaire. The health-related questions included GI medication intake, smoking, alcohol, caffeine, regular exercise, self-cognitive health level, GI symptom, non-steroidal anti-inflammatory drugs (NSAIDs) intake, and sleep problems. In questions about GI medication intake, drugs included digestives and antacids. And the intake of GI drugs more than once during the past 1 month was regarded as taking GI drugs. The sociodemographic questions included age, gender, grade, number of close friends, extracurricular activities, and school performance. The overall prevalence for taking GI drugs, including antacids and digestives, was 17.4 %. When students taking GI drugs were compared with those not taking GI drugs, the former group showed higher rates of girls (P < 0.001) and participants in extracurricular activities (P < 0.05) than the latter group. Factors including alcohol, caffeine, self-cognitive health levels, and GI symptoms showed statistical significance with the rate of GI drug intake. The rate of GI drug intake in NSAID users was 2.7 times higher than that in non-users (P < 0.001). The prevalence rate of every sleep problem was higher in students taking GI medications except snoring, witnessed apnea, and teeth grinding. From the multiple regression, it was found that gender (female), extracurricular activities, alcohol intake, self-cognitive health levels, NSAIDs intake, and nightmares were related factors to GI drug intake. Based on the results, it was conclude that encouragement to build healthy lifestyle habits in adolescents is very important for their academic performances and health status in adulthood.

Comparison of budesonide and dexamethasone for local treatment of oral chronic graft-versus-host disease.

PURPOSE: The results of a prospective study of topical budesonide versus topical dexamethasone therapy for oral manifestations of chronic graft-versus-host disease (cGVHD) are presented. METHODS: In a prospective single-center investigation, a cohort of patients who developed oral symptoms of cGVHD after allogeneic stem cell transplantation were assigned to topical treatment with 0.03% budesonide rinse (group A, n = 26) or 0.01% dexamethasone rinse (group B, n = 24). Diagnosis of oral cGVHD symptoms, clinical staging, and treatment response scoring were performed at baseline and one month later according to current National Institutes of Health consensus criteria. RESULTS: At one-month follow-up, there was a significant decrease in the median oral cGVHD examination score in both groups (p < 0.001); the decrease in the median examination score was greater with budesonide versus dexamethasone therapy (2.5 points versus 1.0 point, p = 0.045). The rates of overall treatment response, including complete and partial responses, were 53.8% and 29.2% in groups A and B, respectively (p = 0.093). In addition, there was a significant decrease from baseline in the median self-rated oral pain severity score in group A (p < 0.001). CONCLUSION: Patients who received topical budesonide or dexamethasone rinse to treat oral manifestations of cGVHD had decreased cGVHD severity and pain scores after 30 days compared with baseline scores, though no statistical differences were seen between groups.

The development of a korean drug dosing database.

OBJECTIVES: This report describes the development process of a drug dosing database for ethical drugs approved by the Korea Food & Drug Administration (KFDA). The goal of this study was to develop a computerized system that supports physicians' prescribing decisions, particularly in regards to medication dosing. METHODS: The advisory committee, comprised of doctors, pharmacists, and nurses from the Seoul National University Bundang Hospital, pharmacists familiar with drug databases, KFDA officials, and software developers from the BIT Computer Co. Ltd. analyzed approved KFDA drug dosing information, defined the fields and properties of the information structure, and designed a management program used to enter dosing information. The management program was developed using a web based system that allows multiple researchers to input drug dosing information in an organized manner. The whole process was improved by adding additional input fields and eliminating the unnecessary existing fields used when the dosing information was entered, resulting in an improved field structure. RESULTS: A total of 16,994 drugs sold in the Korean market in July 2009, excluding the exclusion criteria (e.g., radioactivity drugs, X-ray contrast medium), usage and dosing information were made into a database. CONCLUSIONS: The drug dosing database was successfully developed and the dosing information for new drugs can be continually maintained through the management mode. This database will be used to develop the drug utilization review standards and to provide appropriate dosing information.

Interaction between warfarin and Korean red ginseng in patients with cardiac valve replacement.

BACKGROUND: The objective of this study was to determine whether an interaction exists between warfarin and Korean red ginseng. METHODS: A prospective, double-blind, randomized, two-period crossover study was conducted on 25 patients with cardiac valve replacement under warfarin therapy. Either Korean red ginseng 1 g or placebo (hop extract 0.25 g, caramel color 0.05 g, and red ginseng flavor 0.03 g) was concomitantly administered with warfarin. INR and warfarin concentrations were analyzed on the 3rd and 6th weeks of each study period. RESULTS: The INR changes on the 3rd and 6th weeks of Korean red ginseng administration were -0.16±0.95 and -0.14±0.94 whereas those of placebo were -0.03±0.65 and 0.25±0.95; there were no statistically significant differences in mean INR changes. CONCLUSION: Korean red ginseng could be used with close monitoring and under appropriate education in patients who take warfarin.

Effects of scoparone on dopamine release in PC12 cells.

The effects of scoparone on dopamine release in PC12 cells were investigated. Scoparone at 50-200 microM increased dopamine release into the culture medium. However, the released levels of dopamine by scoparone were not altered in the absence of extracellular Ca(2+) and by adenylyl cyclase inhibitor MDL-12,330A. Scoparone increased phosphorylation of PKA, CaMK II and synapsin I. Scoparone also enhanced K(+)-induced levels of dopamine release by CaMK II phosphorylation. These results suggest that scoparone increases dopamine release by synapsin I phosphorylation via activation of PKA and CaMK II, which are mediated by cyclic AMP levels and Ca(2+) influx.

Effects of berberine on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and a rat model of Parkinson's disease.

Protoberberine isoquinoline alkaloids including berberine inhibit dopamine biosynthesis and aggravate l-DOPA-induced cytotoxicity in PC12 cells. In this study, the effects of berberine on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in PC12 cells and on unilateral 6-OHDA-lesioned rats were investigated. In PC12 cells, berberine at 10 and 30µM associated with 6-OHDA (10, 20, and 50µM) enhanced cytotoxicity at 48h compared to 6-OHDA alone, indicated by an increase in apoptotic cell death. In addition, treatment with berberine (5 and 30mg/kg, i.p.) for 21 days in 6-OHDA-lesioned rats markedly depleted tyrosine hydroxylase-immunopositive cells in the substantia nigra as compared to berberine-untreated rats. Further, the levels of dopamine and norepinephrine were also significantly decreased by berberine administration (5 and 30mg/kg) in the striatal regions of 6-OHDA-lesioned rats. These results suggested that berberine aggravated 6-OHDA-induced cytotoxicity in PC12 cells, and led to the degeneration of dopaminergic neuronal cells in the substantia nigra of 6-OHDA-lesioned rats. It is, therefore, suggested that the use of long-term l-DOPA therapy with isoquinoline derivatives including berberine may need to be examined for the presence of adverse symptoms.