Earticle

The family of bile acids belongs to a group of molecular species of acidic steroids with very peculiar biological characteristics. They are synthesized by the liver from cholesterol through several complementary pathways and secreted into small intestine for the participation in the digestion and absorption of fat. The bile acids are mostly confined to the territories of the so-called enterohepatic circulation, which includes the liver, the biliary tree, the intestine and the portal blood with which bile acids are returned to the liver. In patients with bile acid malabsorption, the amount of primary bile acids in the colon is increased compared to healthy controls. Although the increase in the secondary bile acids including deoxycholic acid, is reported to have the potency to affect tumorigenesis in gastrointestinal tracts, there is no firm evidence that clinically relevant concentrations of the bile acids induce cancer. The list of their physiological roles, as well as that of the pathological processes is long and still not complete. There is no doubt that many new concepts, pharmaceutical tools and pharmacological uses of bile acids and their derivatives will emerge in the near future.

Incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide delay gastric emptying, increasing satiety, and enhance insulin secretion. Two new classes of treatments related to incretin hormones for the management of type 2 diabetes mellitus have emerged: GLP-1 receptor agonists (e.g., exenatide, liraglutide) and the dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin, saxagliptin, vildagliptin, alogliptin), which prevent the degradation of GLP-1. A MEDLINE search was conducted in order to evaluate the efficacy and safety of incretin-based therapies and publications were reviewed. Data from clinical trials indicated incretin-based treatment showed clinically significant reductions in hemoglobin A1c with low risk of hypoglycemia. Weight reductions were observed with GLP-1 receptor agonists where as DPP-4 inhibitors are weight neutral.

The objective of this study was to evaluate the recognition and performance rates about the safety rules on hazardous drugs among the selected pharmacists. The 160 pharmacists working in 4 general hospitals and in the other 4 institutions specialized in the oncology division were surveyed through mail. Among the 137 respondents to the survey (response rate 85.6%), 111 pharmacists (81%) had recognized the terms of ‘azardous drugs’ In categories of vaccines and hormones, the degrees of the recognition rate were much lower than the cytotoxic medications. It was surveyed that the degree of recognition and performance of safety rules on injectable drugs were higher than the disposal and noninjectable medications. The higher recognition rate of the safety rules made the higher degree of performance. These results were expected to provide the incentive for guidelines on handling hazardous drugs based on Korean healthcare system.

Population pharmacokinetics for gentamicin were compared with 20 Korean patients (14 male and 6 female) and 25 Caucasian appendicitis patients (16 male and 9 female). Two to six blood specimens were collected from all patients at the following times : just before a regularly scheduled infusion and at 0.5 hour after the end of a 0.5 hour infusion. Nonparametric expected maximum(NPEM) algorithm for population modeling was used. The estimated parameters were the elimination rate constant(K), the slope(KS) of the relationship between K versus creatinine clearance(Ccr), the apparent volume of distribution (V), the slope(VS) of the relationship between V versus weight, gentamicin clearance(CL) and the slope(CS) of the relationship between CL versus Ccr and the V. The output includes two marginal probability density function(PDF), means, medians, modes, variance, skewness, kurtosis, and CV%. The mean K(KS) were 0.402±0.129 hr-1 (0.00486±0.00197 [hr·mL/min/1.73 m2]-1) and 0.425±0.137 hr-1(0.00432±0.00168 [hr·mL/min/1.73 m2]-1) for Korean and Caucasian populations, respectively. The mean V(VS) were not different at 14.3±3.69 L(0.241±0.0511 L/kg) and 15.8±4.81 L (0.236±0.0531 L/kg) for Korean and Caucasian populations, respectively (P>0.2). The mean CL(CS) were 5.68±1.69 L/hr (0.0714±0.0222 L/kg[hr·mL/min/1.73 m2]) and 6.29±1.84 L/hr (0.0629±0.0189 L/kg[hr·mL/min/1.73 m2]) for Korean and Caucasian populations, respectively. There are no differences in gentamicin pharmacokinetics between Korean and Caucasian appendicitis patients.

Medication adherence is an important public health issue. This study is conducted to explore non-adherence of elderly with hypertension and/or diabetes mellitus and to better understand its' influencing factors. To explore non-adherence, 605 elderly patients in community were surveyed with Modified Morisky Scale (MMS), from Aug 18 to Sept 19, 2008. MMS is designed to predict medication-taking behavior and outcomes, and also to explain persistence of the patient’ long-term continuation of therapy, which is a significant factor in the long-term management of chronic diseases. Also, MMS is designed to classify patients into a high/low continuum for knowledge and motivation. Patients self reported medication adherence were average 4.66 with MMS (range 0-6), only 78% of patients hold high motivation of medication adherence although 95.5% of patients hold high knowledge of medication adherence. This study explores which factors influence to high motivation of medication adherence and it proved that patients' participation in work, education level, participation in private health insurance, number of medication and medication frequency per day, pharmacists' explanation, experience of non adherence due to cost are important factors to explain high motivation of medication adherence of elderly with hypertension and/or diabetes mellitus.

Health Insurance Review & Assessment Service (HIRA) claims database has a high potential to detect signals of new drug interactions. The aim of this study was to evaluate the usefulness of information component (IC) and relative risk (RR) as a tool for signal detection, and to analyze the possible drug interactions caused by clopidogrel using HIRA claims database. This study was performed in elderly patients over 65 years of age who administered clopidogrel from January 2005 to June 2006 in South Korea. Serious Adverse Events (SAEs) as drug interactions of clopidogrel were defined as any ambulatory hospitalization for ischemic diseases within comcomitant medication period of clopidogrel. Information Component (IC) and Relative Risk (RR) were calculated to compare the proportion of drug-SAE pairs in order to select drug specific SAEs. IC and RR signals of clopidogrel drug interaction were screened when IC’ 95% confidence interval was greater than 0 and RR’ 95% confidence interval was greater than 1 respectively. All detected signals were compared to references such as Micromedex® and 2010 Drug Interaction Facts™ Sensitivity, specificity, positive predicted value and negative predicted value were used to evaluate usefulness of this method. Among 13,252,930 cases of elderly patients who co-administered clopidogrel and other drugs, 47,485 cases were detected as SAE. Of these, one-hundred nine cases were detected by the IC-based data-mining approach and ninety one cases were detected by the RR-based data-mining approach. Total One-hundred sixty three unrecognized signals were detected by IC or RR. Twelve signals from IC-based data-mining (57.1%) were corresponded with drug interactions from references and eight signals from RR-based data-mining (38.1%) were corresponded with drug interactions from references. These signals include proton pump inhibitors, calcium channel blockers and HMG CoA reductase Inhibitors, which were known to affect CYP450 metabolism. Further studies using HIRA claims database are necessary to develop appropriate data-mining measure.

The perception of the 20 adverse events of targeted therapy for metastatic renal cell carcinoma was compared among medical professionals. Thirty-seven oncologists, 167 nurses and 79 pharmacists participated in the survey, and the response rate was 61.9%, 98.2%, 84.9%, respectively. Results showed that the most serious adverse event was GI perforation (8.83 points, 10 being the most serious), whereas the least serious was anemia (5.32 points). There were significant differences among oncologists, nurses and pharmacists especially for the moderately-serious adverse event such as wound-healing complication and lymphopenia. Adverse Events Composite Score (AECS) for each targeted therapy was calculated by multiplying adverse event incidence rate and seriousness score. Sunitinib had the highest score at 6.86 point and bevacizumab had the lowest at 2.1. Among professional groups oncologists showed the lowest AECS, whereas nurses had the highest. The gap on the perception of the adverse events among medical professionals needs to be reduced to get better outcomes of medical therapies for cancer patients.

While multiple medication is an important global medication safety issue, ununified concomitant medication by multiple prescriptions may cause more severe problems by the fact that those are neither intended nor watched. This could cause therapy duplication and severe drug interaction and etc. Korean Government made region wide scale programs twice to detect such problems and give warnings to pharmacists and doctors through the internet system in 2009-2010, which are called Drug Use Review Services Pilot Project. This study is an analysis and comparison of the results of the two DUR pilot projects. There were 5.0 and 4.2 cases of severe drug interaction by the concomitant medication of multiple doctors' prescriptions per 10 thousand prescriptions, while only 0.37 and 0 cases by the medication of same doctor's prescription(s). There were 426 and 381 cases of drug duplication by the concomitant medication of multiple doctors' prescriptions per 10 thousand cases, while only 197 and 23 cases by medication of same doctors' prescription(s). Doctors‘participation to those projects improved at Jejudo the later one compared to Goyangsi the former, which means the efforts of them to make less prescription problems succeeded to decrease the number of cases caused from same doctor's prescription. But they could not decrease the number of problem cases caused from concomitant medication by multiple doctors prescriptions enough. The findings support the issue of strengthening and widening the project nation wide and the issue of recommending the patients to designate their own pharmacy, which can provide them counseling for unified and safety controlled medication.

에토포시드와 아피제닌의 약동학적 상호작용 연구를 위하여 아피제닌 (0.4, 2.0 또는 8 mg/kg)과 에토포시드의 경구(6 mg/kg) 및 정맥 (2 mg/kg) 투여 하여 본 연구를 실시하였다. 아피제닌이 cytochrome P450 (CYP) 3A4 활성과 P-glycoprotein (P-gp)의 활성에 미치는 영향도 평가하였다 아피제닌의 CYP3A4의 50% 효소활성억제는 1.8 μM 이었다. 아피제닌은 MCF-7/ADR 세포의 로다마인-123 세포 축적을 증가 시키므로 P-gp를 억제시켰다. 아피제닌은 에토포시드의 혈장곡선하면적과 최고혈장농도 (AUC and Cmax)를 유의성 있게 증가시켰으나, 에토포시드의 최고혈장농도 도달시간 (Tmax)과 생물학적 반감기 (t1/2)에는 영향을 미치지 않았다. 따라서, 아피제닌 존재하에 에토포시드의 절대적생체이용률 (AB)은 대조군과 비교하여 유의성있게 증가되었다. 경구투여시와는 대조적으로, 아피제닌은 정맥 내로 투여된 에토포시드에서는 약동학적 파라미터에 어떤 영향도 미치지 않았다. 따라서 아피제닌이 에토포시드의 생체이용률을 증가시킨 것은 아피제닌이 소장과 간장에서 CYP3A4을 억제 및 소장에서 P-gp를 억제 시켰기 때문으로 사료된다.

Objective: Although recombinant human erythropoietin (rhEPO) has revolutionized the treatment of anemia in chronic kidney disease (CKD) receiving hemodialysis (HD) with no need of blood transfusion, some patients have a blunted or appear to be resistant to rhEPO. There is a controversy in the causes of rhEPO resistance in maintenance HD patients with anemia. This study is to examine current anemia treatment outcomes and the factors influencing the rhEPO responsiveness in HD patient with CKD. Methods: The clinical parameters or factors relating to erythrompoietin treatment outcomes and erythropoietin responsiveness were collected from the HD patients in two large dialysis centers for three months. The collected paramenters included serum iron, total iron biding capacity (TIBC), transferrin saturation rate, ferritin, albumin, intact PTH, C-reactive protein (CRP), nPCR and medications such as an angiotensin converting enzyme inhbitor, an angiotension II receptor blocker and an HMG-CoA reductase inhibitor (HMG-CoA RI). The data were analyzed to examine the degree of acheiveing the anemia treatment goal and factors relating to ERI. Results: Among total 111 patients, 42 (42.3%) and 47 (37.8%) patients achieved the target Hct and Hb based on the Health Insurance Review and Assessment Services (HIRA) reimbursement criteria. In the higher ERI group (upper quartile), the patients had higher CRP levels (0.5 mg/dl) (p=0.0096), and lower TIBC score (<240 μg/dl) (p=0.0027), and less patients were taking HMG-CoA RI (p=0.0019). Male patients (p=0.0204), patients with high TIBC score (R2=0.084, p=0.0021) and patients taking HMG-CoA RI (p=0.0052) required to administer less dose of rhEPO meaning higher erythropoietin responsiveness. Conclusion: Less than 50% of CKD patients were achieving the goals of anemia by erythropoietin administration in large hospitals in Korea even though the goals were lower than those of NKF-K/DOQI practice guideline. The factors influencing ERI were sex, TIBC and HMG-CoA RI administration status, and neither an ACEI nor an ARB did not influence ERI.

The purpose of this study was to evaluate the clinical efficacy of a standardized special ethanol extract from Gynostemma pentaphyllum as a management for anxiety and stress of normal population. This is a two-arm, parallelgroup, randomized, double blind clinical trial comparing Gynostemma pentaphyllum extract 200 mg bid (GP-EX, n=48) or placebo bid (n=54). The main outcome measures were the decrease in anxiety sensitivity index (ASI), the State version (S-STAI) of the Stait-Trait Anxiety Inventory (STAI) and the Trait version (T-STAT) of the STAI from baseline over a 6 weeks treatment period. In more anxious group (S-STAI50 or ASI19), the anxiety in group with GP-EX was decreased significantly than one in normal population with placebo [S-STAI50: T-STAI = from 57.7 ± 6.5 (mean ±S.D.) to 46.8 ± 11.2 in normal population with GP-EX, p=0.002 vs. from 54.1 ± 9.9 to 49.0 ± 9.6 in normal population with placebo, p>0.05; ASI19: T-STAI = from 47.2 ± 12.0 to 42.4 ± 11.1 in normal population with GP-EX, p=0.022 vs. from 48.7 ± 11.5 to 46.0 ± 10.4 in normal population with placebo, p>0.05]. The most frequently reported adverse reactions considered possibly related to treatment were mild gastrointestinal events. GP-EX is more effective than placebo and is well tolerated as a therapy for anxiety and stress of normal population.

In order to minimize such adverse drug reactions, governments and international organs have been on the watch for them. Also in South Korea, a system has been established in order that adverse drug reactions may be reported to Korea Food and Drug Administration(KFDA). This study is to analyze drugs to cause adverse reactions, the adverse reactions and patients concerned on the authority of the data of Korea FDA, which is expected to be the preliminary data on preventable adverse reactions. This study was conducted on the 74,037 cases of adverse drug reactions reported to Korea FDA between January 2007 and June 2010. Fentanyl, iopromide and tramadol caused adverse reactions with high frequencies. Oseltamivir showed a high frequency between 2009 and 2010 due to the influence of the new influenza A. Also, OTC drugs accounted for approximately 5% of the adverse reactions. In 2009, adverse drug reactions remarkably increased (2,106 cases; 10.1%) in infants and children due to the new influenza-A(H1N1). The patients aged between 31 and 64 accounted for approximately 55% during the given period. There was no significant intergender difference. In relation to regions, the adverse reactions most frequently occurred in the gastrointestinal system and the integumentary system for three and half years. In addition to anticancer drugs and immunosuppressive drugs that are known to cause adverse reactions frequently, not a few of OTC drugs and external preparations caused such reactions. In particular, the drugs containing specific ingredients caused adverse reactions more frequently than others from 2007 until the first half of 2010. It is advisable for prescribers to acquaint themselves with such adverse reactions and to prescribe drugs other than them. They also have need to sensibly cope with adverse drug reactions just in case they have no substitute drugs. In addition, patients also need to be trained to understand possible adverse reactions in order that they can sensibly accommodate them or choose healthcare services. The results of this study are expected to be helpful to minimize adverse drug reactions.

The objective of this study was to determine whether any pretreatment parameters were associated with pharmacological effect or toxicity parameters after vincristine administration and to describe a mathematical model, which explains the interpatient pharmacodynamic variability. The relationship between patient characteristics and vincristine dose and hematological toxicity were evaluated. 68 pediatric and adolescence patients and 107 adults with acute lymphoblastic leukemia were treated with vincristine 1.5 mg/m2/day IV and other anticancer drugs as scheduled. Complete blood counts and other blood test results were obtained. The input variables were age, gender, weight, lean body weight (LBW), height, body surface area, vincristine dose and total vincristine dose. The outcome measures were nadir values (white blood cells, absolute neutrophil counts, hemoglobin, and platelets); the absolute decrease, relative decrease, and survival fraction of blood cells. Polynomial regression analysis was carried out to determine the other significant covariates. The variability of WBCnadir was modeled with good precision and accuracy with a two-covariate model. This model should be validated and improved on with further clinical data. We believe that such pharmacodynamic modeling should be explored further to determine its performance and clinical relevance compared with modeling using pharmacokinetic parameter.

서론: 본 연구는 불필요한 소화기관용 약제의 처방이 한국에서의 처방전 당 약물 개수를 증가시키는 것과의 연관성을 검토하고자 수행되었다. 연구방법: 연구를 위한 자료로 건강보험심사평가원의 처방전 데이터와 환자의 기타 모든 의료보험 청구데이터를 이용하였고, 두 데이터셋을 연결하여 처방전들을 소화기관용 약제의 필요성에 따라 소화기관질환 그룹, 관절염질환 그룹, 소화기관용 약제 처방이 불필요할 것으로 그 외 질환 그룹으로 구분, 분리하였다. 결과: 처방전 당 약물의 평균 개수의 분포는 세 그룹에서 비슷한 양상을 보였는데, 관절염질환 그룹과 그 외 질환그룹의 거의 절반 이상은 한 개의 소화기관용 약제를 포함하였다. 세 그룹 모두 처방전 당 약물 개수와 처방전 당소화기관용 약제의 개수가 1차 선형관계를 보였다. 그 외 질환 그룹에서는 처방전 당 전체 약물이 평균 6개를 넘는 경우, 적어도 한 개의 소화기관용 약제가 포함되었다. 본 연구는 불필요한 소화기관용 약제를 처방하는 것은 다제처방의 매우 유의한 예측인자임을 보였다. 결론: 향후, 약제 처방전의 질을 향상시키기 위해서는 각각의 약물을, 특히 소화기관용 약제를, 처방 시 약제의 불가피한 필요성에 대해 판단할 수 있어야 할 것이다.

The purpose of this study is to survey on the pharmacists’medication teaching service for topical steroids in regions without separation of dispensary from medical practice. The questionnaire was sent to 199 pharmacists who work in regions without separation of dispensary from medical practice via mail, e-mail or fax. 112 out of 199 pharmacists requested have answered the survey (response rate 56.28%). The questionnaire was composed of 4 categories withdemographic characteristics, generally explained contents, adverse effects and precaution in pregnancy, breastfeeding and children. We analyzed the questionnaire by the 6 items with reference to the practical guidelines for medication teaching service. The medication teaching service for topical steroids in terms of generic name, physical characteristics, efficacy, usage and dosage, warning and precaution has been well provided by pharmacists in regions without separation of dispensary except for means and duration of optimal storage. The majority of pharmacists provided their patients with 4 and more kinds of items (69.64%), but the generally recommended 4 kinds of items such as generic name, efficacy, usage and dosage, warning and precaution were provided in as low as 48.22% of the respondents. These results show that the medication teaching service for topical steroids in terms of means and duration of optimal storage (45.54%) and the generally recommended 4 kinds of items have not been enough provided by pharmacists in regions without separation of dispensary. Taken together pharmacists in these regions should make a proper guideline for medication teaching service that can prevent the adverse effects of topical steroids.

Purpose: There is considerable variability in rates of hospitalization for patients with community-acquired pneumonia (CAP) in part because of physicians’uncertainty in assessing the severity of illness at presentation. The purpose of the study was to examine the current treatment patterns and factors influencing the Pneumonia Severity Index (PSI) and clinical outcomes in the patient with CAP. Method: The retrospective data collection of the patients with CAP was conducted and the data were reviewed. The collected data included demographic, clinical, laboratory and microbiological medical information. All patients were stratified into three risk groups according to PSI: low risk (PSI score I-II), moderate risk (III) and high risk (IV-V) groups. The examined treatment patterns were the appropriateness of admissions, category of antibiotics used. The prognostic factors associated with PSI and clinical outcomes were examined. Results: One hundred and six patients’medical data were reviewed. The overall appropriateness of admissions was low presenting many of patients were admitted or intensely treated in the hospital despite of lower risk of prognosis and treated with intravenous antibiotics instead of oral fluoroquinolones. Primary pneumonia pathogens were Klebsiella pneumoniae (27%) and Streptococcus pneumoniae (21.6%). Mean LOS was 8.5 days and was significantly longer (10.0 days) (p<0.001) in high risk group. The patients with age >65 (p<0.001), diabetes mellitus (p<0.001), mental alteration (p<0.001), and/or PaO2 <60 mmHg (p<0.001) had a tendency to have higher PSI. The prognostic factors associated with longer LOS were age >65 years (p=0.008), mental status alteration (p<0.001), dyspnea (p=0.002) and PSI score(p=0.001). The prognostic factors associated with mortality were congestive heart failure (p=0.038), systolic blood pressure<90 mmHg (p=0.002) and arterial pH <7.35 (p=0.013). Conclusion: Most of patients were found to over-utilize medical service according to appropriateness of admissions. The elderly, mentally altered patients with low PaO2 had higher PSI score with increased risk of LOS. The mortality could be increased in the patient with disease state of congestive heart failure, high blood pressure, and/or acidosis.

The Korean pharmacy education has been facing extraordinary challenges. Clinical pharmacy has been embraced into mainstream in the new curriculum since its introduction in Korea. Although these changes are positive to provide our graduates adequate knowledge and skills to meet international standards of pharmacy education, current preparedness is far from desired goals. Thus, faculty members and clinical pharmacy experts from diverse walks are tirelessly committed to develop clinically oriented educational sites. However, it is important to recognize that pharmacy practice, research, and education should be aligned with the profession°Øs vision. Most faculty members in clinical pharmacy were unexceptionally expected to tackle educational challenges with new curriculum. All academicians must profess throughout their career. Fundamental component in academic career is research accomplishments. The prosperity of clinical pharmacy inevitably goes with research. Clinical researchers in Korea are underprivilaged over basic scientists due to less funding opportunity, administrative support, and research resources. Clinical pharmacy researchers should further overcome poor recognition among other healthcare professionals and government. Aggressive networking and support and awareness of pharmacy oriented clinical research from the Korean college of clinical pharmacy would nurture clinical pharmacy research. With research progress, clinical pharmacy would be prerogative in Korean pharmacy advance.