Earticle

Adverse drug reactions (ADR) including allergy are more preventable if patients recognize. This study was to investigate ADR recognition by patients who visited one university hospital located in Seoul, by face-to-face or telephone interviews using questionnaires. Recognitions, understandings, and managements on ADR in 225 adult patients enrolled in this study, were compared between ADR experienced group (n=89) and no-experienced group (n=137). Common knowledges and direct experiences on ADR were attributable to high perceptions on ADR, and lacking of active communications with clinical professionals to manage ADR was shown. In general, there were no significant differences in ADR perceptions between ADR experienced and no-experienced groups in almost items. This study findings would be useful to discuss clinical solutions for preventing ADR including drug allergy from patient individual level, and strategies including public education, guidebook on drug allergy, patient medication history record, and proactive efforts by professionals to improve ADR perception levels would be suggested.

While Self-monitoring of blood glucose (SMBG) has been recommended in some diabetes mellitus (DM) patients population according to the 2010 American Diabetes Association (ADA), 2007 Korean Diabetes Association (KDA), 2005 International Diabetes Federation guideline, it is excluded from a routine insurance coverage for outpatients in Korea. The objective of this study is to meta-analyze the impact of SMBG on HbA1c in non insulin-treated diabetes mellitus (NIT) DM patients. Published clinical literatures were identified through electronic database searches from inception and until May 2010. Studies were selected if they met the following inclusion criteria: 1) randomized controlled trials (RCTs), 2) comparing SMBG with non-SMBG in NIT type 2 diabetes, 3) measuring HbA1c as an outcome. Literature qualities were assessed by the Scottish Intercollegiate Guidelines Network Checklist. The mean difference of HbA1c between the 2 groups was pooled from non-heterogeneous 6 RCTs by meta-analysis using Review Manger (RevMan) Version 5.0 program. Pooled results demonstrated that SMBG is associated with a statistically significant improvement in glycemic control (mean HbA1c difference -0.23, 95%CI -0.32, -0.13). Sensitivity analysis showed that glycemic controls were significantly improved in patients with shorter study duration, more frequent self-monitoring, higher baseline HbA1c value, and without prior SMBG experiences. Conclusively SMBG is effective in improving glycemic control in NIT DM patients, but additional evidences from further researches in Korean patients and cost-effectiveness analysis would be necessary to make a suggestion for coverage expansion.

Tacrolimus, an immunosuppressant prescribed against graft-versus-host disease (GVHD) in patients with allogeneichematopoietic stem cell transplantation (HSCT), is affected to change its pharmacokinetic properties by various factors. For this reason, it is needed a close monitoring to adjust dosage amount in order to optimize the blood concentration of tacrolimus is located within the effective range. According to our in-house study, 62% of HSCT-patients were needed dosage-adjustment and it is necessary to optimize the current immunosuppressive regimen in clinical settings. A retrospective study was designed to evaluate the dosing regimen (converting ratio of IV:PO=1:4) of tacrolimus in HSCT patients (n=62). After collecting data from patient’s profile and medical record, pharmacokinetic parameters were calculated and compared between the estimated and the actual values in the selected subjects (n=58). It was found that the bioavailabilty (BA) of oral tacrolimus was 40.5% very much different from that is known as 25%. It implies that the current protocol has a potent risk causes dose-related toxicities to the patients. Furthermore, analyses among factors demonstrated that there was no statistical significance between BA of tacrolimus and the variable factors. In the clinical perspectives, the current converting ratio of tacrolimus in patients with HSCT to be re-considered and an appropriate and optimal alternative regimen should be adopted to prevent GVHD and to increase the quality of life of patients.

The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of nimodipine in rats. Pharmacokinetic parameters of nimodipine were determined in rats after oral administration of nimodipine (16 mg/kg) with or without ticlopidine (3 or 10 mg/kg). Ticlopidine inhibited cytochrome P450 (CYP)3A4 activity. Ticlopidine significantly (p<0.05, 10 mg/kg) increased the area under the plasma concentration-time curve (AUC) of nimodipine and ticlopidine significantly (p<0.05, 10 mg/kg) prolonged the terminal half-life (t1/2) of nimodipine. Ticlopidine significantly (p<0.05, 10 mg/kg) decreased the total body clearance (CLt). The absolute bioavailability (AB%) and relative bioavailability (RB%) of nimodipine by presence of ticlopidine were increased by 14% and by 42%, respectively, compared to the control. Based on these results, the increased bioavailability of nimodipine might be due to inhibition of the metabolizing enzyme cytochrome P450 (CYP)3A4 in the liver or intestinal mucosa and/or reducing total body clearance by ticlopidine.

The prescription sheets for outpatients from July 2008 to June 2009 from 7 community pharmacies in Ulsan City were surveyed for the anti-inflammatory drug (AID) prescription pattern. The AID prescription rate of pediatricians and ENT physicians were 30.0% and 34.8%, respectively. The oral steroidal anti-inflammatory drugs (SAIDs) were prescribed as much as 3.9% by pediatricians and 10.3% by ENT physicians. The chiefly prescribed oral SAID was prednisolone in pediatric clinics and methylprednisolone in ENT clinics. Meanwhile the prescription rate of oral non-steroidal antiinflammatory drug (NSAID) was 22.5% by pediatricians and 21.4% in ENT physicians. The most favorable NSAIDs were propionate derivatives in both clinics. In case of externally-applied SAIDs, the prescription rate of pediatricians was 3.6% and that of ENT physicians was 2.8%. Among them, nasal spray, inhalant and gargle formulations for upper respiratory infection (URI) treatment occupied 35.8% of externally-applied SAIDs in pediatric linics and 59.7% in ENT clinics. Further, it was observed that ENT physicians favored much stronger SAIDs in Group III of ATC classification (75.4% of externally-applied SAIDs) than pediatricians (49.2%). In the survey of AID combination rate, pediatric clinics showed much lower rate (1.4% of total AID prescriptions) than ENT clinics (7.5%). Among them, the combination rate of oral SAID and oral NSAID by ENT physicians (52.2% of total AID combinations) was much higher than pediatricians (36.6%), which might be over-prescription of AID agents. In conclusion, the AID prescription rate as well as AID combination rate, especially in SAID prescriptions, was much higher in ENT than pediatric clinics, which implies the higher confidency on AID drugs of ENT physicians even though the severity of patient's symptom could be considered.

Therapeutic duplication (TD) is a serious problem that frequently occurring primarily in the ambulatory setting in Korea. Implementation of concurrent drug utilization review (DUR) is a promising way to reduce inappropriate prescription and dispensing, and improve patient safety. This study was aimed to develop the process of DUR module of TD. Sixty-five drug ingredients classified into the drug category of the antipyretic, analgesic, and anti-inflammatory drug pproved in Korea (The KFDA-dess nated classification codes of 114 or 264) were reviewed for this purpose. The drug ingredients (and products) were reclassified based on WHO's Anatomical, Therapeutic and Chemical (ATC) classification system. The clinical practice guidelines, textbooks and product labels on therapeutic uses of these drugs in Korea and several fores n countries were reviewed. If the drugs were categorized into the same therapeutically duplicable class, they were defined not to be used concurrently because the concurrent use was “therapeutically duplicated (unnecessary or even harmful)”. Among the studied drug products, the following 5 drug classes were considto beas “therapeutic duplication”: (1), on-t tooid DURnti-inflammatory drugs (NSAIDs, including s Dicylates), (2),Anilidts, (3),Opioids, (4) Ergot Dk Doids and (5) 5-HT1 receptor agonot s. Therefore, concurrent prescribing or dispensing of more than 2 drug ingredients any in the above same classes should be considered as TD and needed to be warrant for careful review by pharmacists before dispensing.

In 2009, American Journal of Health-System Pharmacy (AJHP) recommended that targeting vancomycin trough concentrations of 10 mg/L or more because of therapeutic failure and potential risk of developing vancomycin resistance. Therefore, new dosage guidelines that could achieve to these higher target were needed. The aims of this study were to develop dosage guidelines targeting new vancomycin trough concentration and to evaluate the performance of these new guidelines. All data analysis were performed using NONMEM®. Population pharmacokinetic model was first developed from vancomycin dosage and concentration data collected retrospectively during routine therapeutic drug monitoring in 441 patients, then new vancomycin dosage guidelines were developed by using the model to predict vancomycin trough and peak concentrations in a simulated dataset. The estimates, such as, vancomycin concentration trough level, time to achieve target level, mean error were performed to evaluate and compare difference between conventional dosage and new dosage guidelines. The proposed dosage guidelines were predicted to achieve 43.5% of vancomycin trough level within 10~20 mg/L, which is significantly higher than current guidelines (26.3%). Time to achieve target trough level was 19.4 hours in new guidelines comparing to 93.1 hours in the conventional dosage. Thus, new vancomycin dosage guidelines have been developed to achieve new target trough concentrations earlier and more consistently than conventional guidelines.

섬유근통 증후군은 만성 전신 통증을 나타내며 피곤, 두통, 우울증, 수면장애등을 동반하는 질환이다. 주로 30-50대의 여성에게서 많이 나타나며 미국에서 2-4%, 한국에서 2%의 발병률을 보이고 있다. 정확한 원인과 기전이 밝혀져 있지않아서 진단과 치료에 많은 논란과 어려움이 있다. 현재는 증상치료에 목표를 두고 삼환계항우울약을 많이 사용하고 있으나 심각한 부작용의 문제가 있다. 이러한 문제때문에 최근에는 selective serotonin reuptake inhibitor (SSRI) 또는 serotoninnorepinephrine reuptake inhibitor (SNRI)를 빈번히 사용하고 있다. 본 연구는 SNRI의 하나인 milnacipran의섬유근통 증후군 치료에 대한 효능 및 안정성을 알아보기 위해, MEDLINE에 등재된 논문을 기한없이 milnacipran과 fibromyalgia로 검색하여 무작위 배정 및 이중맹검 임상연구자료들을 선별하였다. 선별된 6개의 임상연구 결과, milnacipran를 사용했을때 일관된 효능성과 안정성이 관찰되었고 섬유근통증후군 치료와 그에 수반되는 여러증상에 효과적인것으로 나타났다.

Bambuterol hydrochloride, dimethylcarbamic acid 5-[2-(1,1-dimethylethyl)amino-1-hydroxyethyl]-1,3-phenylene ester hydrochloride, is the prodrug of active β2-adrenergic metabolite terbutaline. The purpose of the present study was to evaluate the bioequivalence of two bambuterol hydrochloride tablets, Bambec® tablet 10 mg (Yuhan Co., Ltd.) and Bambucol tablet 10 mg (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). In vitro release of bambuterol from two bambuterol hydrochloride formulations was tested using KP VIII Apparatus II method with various dissolution media. Twenty eight healthy male Korean volunteers, 23.86±1.65 years in age and 68.98±9.58 kg in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After two tablets containing 10 mg as bambuterol hydrochloride were orally administered, blood samples were taken at predetermined time intervals, and the concentrations of bambuterol in serum were determined using column switching HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as AUCt, Cmax and Tmax were calculated, and ANOVA test with K-BE Test 2002 was utilized for the statistical analysis of the parameters using logarithmically transformed AUCt, Cmax and untransformed Tmax. The results showed that the differences between two formulations based on the reference drug, Bambec®, were -8.10%, -3.82% and 12.65% for AUCt, Cmax and Tmax, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (i.e., log 0.8093~log 1.0302 and log 0.8564~log 1.1280 for AUCt and Cmax, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Bambucol tablet 10 mg was bioequivalent to Bambec® tablet 10 mg.

Controlling inappropriate antibiotics prescribing for acute upper respiratory infections(URI) is a very important for prudent use of antibiotics and resistance control. Health Insurance Review and Assessment Service (HIRA) introduced Prescribing Evaluation Program and publicly reported antibiotics prescribing rate for URI of each health institution. We performed segmented regression analysis of interrupted time series to estimate the effect of public report on antibiotics prescribing rate using national health insurance claims data. The results indicate that just before the public report period, clinics' monthly antibiotics prescribing rate for URI was 66.7%. Right after the public report, the estimated antibiotics prescribing rate dropped abruptly by 12.3%p. There was no significant changes in month-to-month trend in the prescribing rate before and after the intervention.

본 연구에서는 anthracyclines의 심장 독성을 예방하기 위해 사용되는 dexrazoxane의 가장 적절하고 안전한 용량을 평가하고자 했다. 이 약물은 같은 적응증에도 불구하고 미국과 유럽에서 두 배 차이가 나는 용량으로 허가 받아 사용되고있다. 그러므로 dexrazoxane의 anthracycline로 인한 심독성의 예방에 관한 논문을 찾아 dexrazoxane : doxorubicin = 20: 1의 비율로 사용했을 경우와 10:1로 사용했을 때의 효과와 부작용을 비교 하였다. 이 두 가지 용량으로 진행된 모든 임상 연구에서 dexrazoxane이 doxorubicin의 심독성 예방에 통계적으로 유효한 효과가 있다고 결론 내렸다. 또한 dexrazoxane의 추가 요법으로 인해 Tumor effect의 차이를 비교 분석한 결과, 두 가지 용량 모두에서 dexrazoxane이 doxorubicin의 항암 효과에 영향을 미치지 않는 것으로 분석되었다. 대부분의 연구에서 dexrazoxane의 약물 자체의 부작용은 분석하지 않았지만, dexrazoxane:doxorubicin을 20:1의 비율로 사용했던 한 연구에서 dexrazoxane군에서 부작용이 있음이 평가되었다. 반면, dexrazoxane의 용량을 doxorubicin 용량에 비해 10:1로 사용한 모든 연구는, 대상 환자군이18세 이하의 소아 청소년으로 이 용량을 성인에게도 적용할 수 있는지에 대한 추가 연구가 필요하다. 그러나 항암제의 경우, 대부분 환자의 체표면적(BSA)을 기준으로 약용량을 결정하며, 이는 일반적으로 10세 이상이 되면 어른의 체표면적 의 70% 정도가 된다. 그러므로, 본 연구에서는 통계적으로 충분한 수의 10세 이상의 소아, 청소년에게 doxorubicin으로 인한 심독성 예방 효과가 입증되었던 dexrazoxane: doxorubicin을 10:1의 용량으로 사용하여도 임상적인 효과를 기대 할 수 있으며, 이 용량은 dexrazoxane 자체의 유해반응도 감소시킬 수 있을 것이라고 결론 맺는다.

Cefprozil is a broad-spectrum oral beta-lactam cephalosporin consisting of cis- and trans-isomeric mixture whose ratio is approximately 90:10. Cefprozil is used to treat certain infections caused by bacteria such as bronchitis and ear, skin, and throat infections. The purpose of the present study was to evaluate the bioequivalence of two cefprozil tablets, Cefzil® tablet 250 mg (BMS Pharmaceutical Korea., Ltd.) and Procezil tablet 250 mg (Hanmi Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of cefprozil from the two cefprozil formulations were tested using KP VIII Apparatus I method with water dissolution media. Thirty five healthy male subjects, 24.00±1.53 years in age and 69.77±9.99 kg in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After four tablets containing 1000 mg as cefprozil were orally administered, blood samples were taken at predetermined time intervals and the concentrations of cefprozil in serum were determined using HPLC/UV detector. The dissolution profiles of two formulations were similar in water tested dissolution media. The pharmacokinetic parameters such as AUCt, Cmax and Tmax on the basis of total-cefprozil were calculated, and computer program (K-BE Test 2002) was utilized for the statistical analysis of the parameters using logarithmically transformed AUCt, Cmax and untransformed Tmax. The results showed that the differences between two formulations based on the reference drug, Cefzil® tablets, were -0.81%, -3.00% and -6.83% for AUCt, Cmax and Tmax, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.9515~log 1.0454 and log 0.9613~log 1.0465 for AUCt and Cmax, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Procezil tablet was bioequivalent to Cefzil® tablet.

Therapeutic duplication of prescriptions is the most frequently reported inappropriate drug use in Korea. To prevent significant problems during drug prescribing and dispensing, prospectively, development of standard including drug lists considered as therapeutic duplications for the prioritized drug classes first would be necessary. This study was aimed to analyze frequent drug classes of therapeutic duplications by healthcare providers in clinical practice settings. National health claims data for drug review and reimbursement (1,426,065 prescriptions dated March 19, 2008) were analyzed. Therapeutic duplication was defined as the prescription including more than 2 ingredients belonging to the same KFDA drug classification numbers that considered to have therapeutic similarities. The following 3 drug classes were mostly frequent therapeutic duplication classes: 114 anti-pyretics, analgesics and anti-inflammatory drugs; 117 drugs for psycho- nervous system; 141 Antihistamines. About 3.5% of overall prescriptions analyzed showed therapeutic duplications. This result might be starting step to develop DUR therapeutic duplication standard.

This study was conducted to analyze the cost-utility of ramosetron monotherapy, trimebutine monotherapy and trimebutine+ loperamide combination therapy in male diarrhea-predominant patients with irritable bowel syndrome (IBS) in Korean healthcare setting. We constructed a decision-analytical model to estimate both total costs for each state of health and outcomes such as IBS-symptoms improvement for 3 and 6 months time horizon. Base analysis found that for ramosetron treatment with the price of KW910 for 5 μg tablet, incremental cost effectiveness ratios (ICERs, cost per quality-adjusted life day) were KW85,000 and KW62,000 for 3 months and 6 months, respectively, compared with trimebutine. But ramosetron was a dominant strategy when compared with trimebutine+loperamide for both 3 months and 6 months. Sensitivity analyses showed robust results for drug acquisition costs till ramosetron price of KW950/tablet. In conclusion, ramosetron was a cost-effective regimen compared with trimebutine or rimebutine+loperamide from the societal perspective.

The main objective of this study is to evaluate the cost-effectiveness of tafluprost compared with latanoprost in primry open Angle Glaucoma (POAG) or ocular hypertension OH patients in Korea. A decision analytic model was developed from a societal perspective to estimate clinical outcome, drug cost and glaucoma related cost. The model assumes branch like following: successful treatment, switching to other drug, adding other drug, laser or surgery. Treatment successrate is defined as the percentage of patients with elevated IOP achieving <20% reduction, and discontinuation rate is the percentage of patients who were withdrawn due to severe adverse events. A model that is comprised of 1 month cycle length has 1 year. Treatment success rate and discontinuation rate were obtained from published literatures searched in database. Resource utilizations and costs were calculated with national health insurance data and clinical expert opinions. Sensitivity analyses were performed on crucial parameters. Tafluprost is less costly than latanoprost, $609.0 vs $651.2 expected cost. Thus tafluprost was shown to be dominant compared with latanoprost. The results of sensitivity analysis revealed stable across most of the included parameters. According to this study, tafluprost shows more clinical outcome for 1 year than latanoprost. In addition, first-line treatment of tafluprost is a more cost-minimizing strategy associated with POAG or OH compared with latanoprost.