Byung Koo Lee

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 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.

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

BackgroundOlder 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).MethodsA 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 R2. Discrimination of the model was assessed by an analysis of the area under receiver operating curve (AUROC).ResultsTwo 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 (χ2 = 3.842, p = 0.871 for model I and χ2 = 8.130, p = 0.421 for model II). The Nagelkerke R2 effect size and AUROC for model I was 0.215 and 0.833, respectively. Model II had the Nagelkerke R2effect size of 0.174 and AUROC of 0.819.ConclusionsThese results suggest that pharmacists’ comprehensive review for pre-operative medication use is critical for the post-operative outcomes like delirium in older patients.

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.

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 18fluoro-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.

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.

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.

Formulation and evaluation of ubidecarenone transdermal delivery systems

Purpose: This study is aimed to examine the feasibility of developing ubidecarenone (coenzyme Q10, CoQ10) 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 (μg/cm2/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. CoQ10 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 μg/cm2/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 CoQ10 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 Cmax, comparable AUC, and prolonged t1/2 and Tmax compared to oral administration of drug. Conclusions: For effective transdermal delivery system of CoQ10, 6% linoleic acid or oleic acid in DGME-PGML (60:40) could be employed.

Development of clinical pharmacy services for intensive care units in Korea

ObjectiveTo be utilized for the development of pharmacists’ intervention service by determining factors which affect pharmacists’ prescription interventions.SettingPatients who were admitted to intensive care units (ICUs) in internal medicine departments in Korea.MethodsData 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 measurePrimary outcome was factors which affect pharmacists’ prescription interventions. Secondary outcomes included frequencies of the intervention, intervention acceptance rates, intervention issues, and frequently intervened drugs.ResultsA 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.ConclusionThe 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.

Pharmacokinetics of Itraconazole in Diabetic Rats

ABSTRACT After intravenous or oral administration of 10 mg/kg itraconazole to rats with streptozotocin-induced diabetes mellitus and to control rats, the total area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24) for itraconazole and that for its metabolite, 7-hydroxyitraconazole, were similar between the two groups of rats. This may be explained by the comparable hepatic and intestinal intrinsic clearance rates for the disappearance of itraconazole and the formation of 7-hydroxyitraconazole in both groups of rats.