Earticle

A computerized chemotherapy order system (CCOS) was developed to improve the accuracy and efficiency of prescriptions for pharmacy medication scheduling at a teaching hospital, Asan Medical Center, Seoul, Korea. We evaluated the system by comparing prescriptions before and after the implementation of the system and by analyzing the effects of the system on dosing accuracy (only against 5-FU), prescription change, overdoses above maximum limit and medication disposal in non computerized program group (control group) and CCOS group. In terms of dosing accuracy, prescription error rate (%) was significantly decreased in CCOS groups compared with the control group. The rate of prescription changes was also significantly decreased in CCOS groups. Regarding overdoses above maximum limit, we found that there was no prescription order exceeding the dosage limit in CCOS groups in contrast to significant overdoses in control group. In terms of medication disposal, there was no significant difference between 2 groups. We suggest that the computerized chemotherapy order system for chemotherapy may bean important and useful tool for minimizing prescribing errors in the hospitals.

지난 20 여 년 간 서구 선진사회에서는 식사장애(Eating disorder) 중에서 신경성 폭식증(Bulimia nervosa)의 발병률이 급격히 상승하였고, 우리나라는 특히 젊은 여성층에서 발병률이 빠르게 상승하고 있다. 치료약물로는 주로 항우울제가 선택되지만, 치료효과가 미흡한 바, 항경련제인 topiramate가 효과가 있다는 보고들이 있어 이를 신경성 폭식증치료에 적극 사용할 수 있는가에 관심이 고조되었다. 본 연구는 topiramate가 지닌 신경성 폭식증 치료효과에 대한 최신 지견을 얻고자, 1990년부터 2006년 사이 MEDLINE과, 한국의학논문데이터베이스에 등재된 국내외 자료를 binge eating disorder, bulimia nervosa, topiramate라는 3개의 주요어휘로 검색하여 추출한 자료중에서, 대조군이 사용된 무작위 배정, 이중맹검 임상연구 및 치험사례 만을 선별하여 임상적유용성을 평가하였다. 국외 임상연구 및 치험사례에 따르면, topiramate가 신경성 폭식증에 수반되는 유해한 증상의 발생빈도를 경감시키는데 유효함을 나타내었다. 국내에는 아직 topiramate의 신경성 폭식증 치료효과를 검증한 체계화된 임상연구나 치험사례가 보고된 바 없었다. 피험자의 규모가 작다는 한계에도 불구하고, 일일 투여량 25 mg로 시작하여 점차 증량후 최대 600 mg까지 투여한 국외의 연구결과는, topiramate가 신경성 폭식증 치료에 유효한 결과를 보인다고 사료되므로, 국내 신경성 폭식증 임상치료와 연구에 반영되기를 기대한다.

The clinical investigations above suggest that topiramate may be an effective agent in the treatment of BED or BN by reducing binging/purging episodes, improving the HRQOL, and decreasing weight. The case report and case series also support these findings. However, there are several limitations in the above studies and cases. All these had relatively small sample size, and two of them were only 10-week-period studies. Optimal duration of treatment with topiramate in patients with BED or BN is unknown. As most clinicians treat the patient with BED or BN for 6 to 12 months and then reassess, at least 6 months period is needed to show its efficacy. One of studies included only women in the patient group. In the case series, all patients had severe comorbid mood disorders such as major depression and bipolar disorder besides BN. Therefore, notwithstanding its clinical usefulness, additional researches are needed to define the role and the benefits of topiramate in the treatment of BED or BN more thoroughly.

Theophylline은 methylxanthine계열 기관지확장제중 가장 강력하며 기관지 천식이나 만성 폐쇄성 호흡기 질환환자에서 사용된다. Theophylline은 치료지수가 5-20 mg/L로 매우 좁은 치료지수를 갖는 약물이다. Cimetidine과 theophylline은 주로 간에 존재하는 cytochrome P450 (CYP) 효소에 의해 대사되며 theophylline은 유전적 다형성이 보고된 바있는 CYP1A2에 의해 대부분 대사된다. 본 연구는 theophylline의 약동학에 미치는 cimetidine의 영향을 평가하고 CYP1A2 유전적 다형성의 영향유무를 검증하였다. 8명의 건강한 비흡연자인 한국인 자원자를 모집하여 공개, 2기 교차시험을 실시하였다. 8명의 자원자에게 1기 시험의 첫날 100 mg의 aminophylline을 경구로 단회 투여하였으며 약물투여 후 36시간까지 채혈하여 혈장을 보관하였다. 공혈장 채취를 위해 채혈한 혈액중 일부를 가지고 유전자형 검색을 실시하였다. 1주일의 휴약기를 거친 후 2기 시험을 진행하였다. 2기 시험의 첫날 같은 용량의 aminophylline과 200 mg의 cimetidine을 같이 경구로 단회 투여하였다. 혈장 중 theophylline농도는 고성능 액체 크로마토그래피를 이용하여 측정하였으며 1기와 2기 시험에서 각종 약동학적 경수를 컴퓨터를 이용하여 계산하였다. 8명의 자원자에서 PCR-RFLP를 이용하여 유전자형 검색을 실시하였다. 8명(남자 4명, 여자 4명)의 자원자에서 약물과 관련한 약물이상 반응은 시험기간동안 발생하지 않았다. 약동학적 분석에서 theophylline의 혈장 농도 곡선하 면적(AUC)와 최고혈중농도()가 cimetidine과 theophylline을 동시에 투여하였을 때 통계적으로 유의하게 증가하였으며 경구 청소율(CL/F)은 유의하게 감소하였다. 8명의 CYP1A2 유전자형 검색에서 돌연변이 유전자형은 발견하지 못하였으며 CYP1A2*1C 유전자형 검색에서 모두 (G/G) homozygote였으며 CYP1A2*1F 유전자형 검색에서는 5명이 (A/A) homozygote이고 3명이 (A/C) heterozygote였다. 따라서 theophylline대사에 CYP1A2유전자형에 따른 대사능의 차이는 관찰할 수 없었다. 이상의 결과를 요약하면 theophylline의 약동학은 cimetidine에 의해 유의한 차이를 보였으며 CYP1A2유전자형에 따른 영향은 관찰할 수 없었다. CYP1A2유전자형에 따른 생체내 대사능을 관찰하는 실험이 향후 이루어 져야 할 것으로 사료된다.

The purpose of the present study was to investigate the effect of cimetidine on theophylline pharmacokinetics in Korean healthy normal subjects. Eight subjects were enrolled and open label, two period cross-over study was conducted without significant drug related adverse reactions. Cimetidine seemed that significantly inhibited the metabolism of theophylline, oral clearance decreased significantly when cimetidine was coadministered. Coadministered cimetidine increased and of theophylline. All subjects were genotyped using PCR-RFLP methods to evaluate the differences in metabolic capacity in accordance with CYP1A2 genotypes, but no mutant genotype was found. This suggests that metabolic capacities were not significantly affected by CYP1A2 genotypes among subjects. In conclusion, disposition of theophylline was significantly affected by coadministered cimetidine. Further evaluation with well-designed drug interaction study in accordance with various genotype of CYP1A2 is needed.

Objectives : It is necessary to monitor consumption of drugs in order to enhance promote appropriate use of drugs. Defined Daily Dose(DDD) of World Health Organization(WHO) has been used for evaluating the amount of medicine use. However, DDD of some drugs must be determined for drugs in Korea which are not listed by WHO. Our formulary follows ourself classification and DDD of some drugs must be determined since they exist only in Korea. This study was aimed to determine DDD value using RAND Appropriateness Methods and evaluate the amount of antibiotics use using DDD value. Methods : J01 antibiotics of WHO anatomical therapeutic chemical(ATC) classification were extracted from drug formulary. Antibiotics list without DDD was identified to determine their DDD with comprehensive review of references and recommendation of experts. defined. Review of reference was executed. of Expert panels were comprised of clinical pharmacist and clinical doctors. Modified Delphi Method was applied by survey and consensus meeting. Amount of antibiotic use was calculated by DDD/1000 inhabitants/day in the national level using health insurance claim data. Results : The result of 1 round, DDD values of 28 ingredients were determined from the first round of consensus meeting. With 2nd round meeting, 3 ingredients were deleted and DDD of 17 ingredients were decided. Analysis of antibiotic use in health insurance claim data showed 22.97 DDD/1000 inhabitants/day in 2003 year. Conclusion : This study can contribute to the establishment of DDD assignment and thus quantifying drug uses.

The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of diltiazem (15 mg/kg) after oral administration of diltiazem with or without atorvastatin (0.5, 1.5 and 3.0 mg/kg) in rats. Coadministration of atorvastatin increased significantly (p<0.05, 3.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration of diltiazem compared to the control group. The total plasma clearance (CL/F) of diltiazem was decreased significantly (p<0.05, 3.0 mg/kg) compared to the control group. The relative bioavailability (RB%) of diltiazem was increased from 1.14- to 1.49-fold. Coadministration of atorvastatin did not significantly change the elimination rate constant , terminal half-life and the time to reach the peak concentration of diltiazem. Based on these results, we can make a conclusion that the significant changes of these pharmacokinetic parameters might be due to atorvastatin, which possesses the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein (P-gp) efflux pump in the intestinal mucosa.

Background: The multitude of the therapeutic usefulness of intra-articular injection of hyaluronate on oateoarthritis of the knee is still in question. The objective of this systemic review was to elucidate both the therapeutic efficacy and the safety of intra-articular administration of hyaluronic acid for degenerative osteoarthritis of the knee joints. Methods: I searched MEDLINE and Korea Medical Database (KMbase) from January 1990 to April 2007 using a combination search terms for knee osteoarthritis and hyaluronic acid and a filter for randomized controlled trials. I extracted data on pain at rest, and during or just after movement, on joint function, and on adverse events. Results: Ten trials that reported usable quantitative information on any of the predefined end points were identified and included in the systemic review. Intra-articular injection of hyaluronic acid can decrease symptoms of osteoarthritis of the knee. The study revealed significant improvements in pain and functional outcomes with few adverse effects. However, there was significant between-study heterogeneity in the estimates of the efficacy of hyaluronic acid. Sub-group analysis showed that lower methodological quality such as a single-blind or single-center design resulted in higher estimates hyaluronic acid efficacy, and that patients older than sixty years of age and those with the most advanced radiographic stage of osteoarthritis were less likely to benefit from intra-articular injection of hyaluronic acid. Conclusion: According to the currently available evidence, intra-articular hyaluronic acid has been proven clinically effective for the patients bearing the knee osteoarthritis with NSAID-induced GI troubles or inapplicable to any surgery, and may be associated with lower risk of adverse events.

This study was aimed to provide the controlled terminology for adverse drug reactions by selecting an appropriate internationally standardized classifications (WHO-ART or MedDRA). We collected the relevant information on ADR terminology systems including WHO-ART and MedDRA by online searching and visiting pharmaceutical companies and WHO UMC (Uppsala Monitoring Centre, Uppsala, Sweden). For MedDRA, project leader directly communicated with the officer of MSSO (Maintenance and Support Services Organization). Collecting all the pertinent information, two possible terminology classifications or systems (WHO-ART and MedDRA) were compared in the views of acceptability, cost-effectiveness and international feasibility and reviewed by the consultation committee and finally WHO-ART was selected.