Earticle

We conducted a single blind, randomized and crossover clinical trial in order to test the effect of curcuma longa herbal mixture on blood alcohol level and alcohol hangover in 19 healthy volunteers. The herbal mixture did not show a statistical significance in Cmax, Tmax and AUC in alcohol disposition. The herbal mixture did not also ameliorate blood laboratory result after alcohol consumption. In contrast, the herbal mixture is shown effective on alcohol hangover. In behavior tests, the fewer subjects in the herbal mixture group were impaired with alcohol than in reference group. Moreover, the symptom severity score in the herbal mixture was lower than that in reference group. The symptom severity score was statistically especially in stomach pain, diarrhea, concentration disorder, memory and bad breath at drinking day and one day after drinking. These results indicate that the general symptoms seemed to be recovered as time goes on. From these results, it was suggested that the herbal mixture have a beneficial effect on modulating alcohol hangover.

Purpose: 본 연구는 한국인 성인 조혈모세포이식환자를 대상으로 경구용 사이클로스포린의 집단약동학 분석을 통하여 사이클로스포린의 약동학적 파라미터에 영향을 미치는 요인 분석을 실시하고자 하였다. Methods: 2000년 12월부터 2006년 8월까지 서울대학교병원에서 동종조혈모세포이식을 받고 면역억제제로 사이클로스 포린을 복용한 성인 백혈병환자를 대상으로 후향적으로 자료를 수집하였다. 사이클로스포린의 약동학에 영향을 미치는 인자로는 연령, 성별, 이식 후 날짜, 신기능, 공여자와의 관계, 질병의 종류, 혈중 빌리루빈 농도, 사이클로스포린의 대사를 유도하는 프레드니솔론의 투여량, 헤마토크리트, 사이클로스포린의 대사를 저해하는 약물의 병용여부 등을 검 토하였다. 분석은 NONMEM® VI 프로그램을 이용하였으며, 변수를 추가하지 않은 기본 모형을 만든 후에 단계적인 요인의 추가와 제거를 통해 최종모형을 제작하였다. Results: 최종 상관 모형은 다음과 같다 CL/F (L/h) = 85.6×e(0.646 × HCT/28.9 + 0.0464 × Gender). 사이클로스포린의 겉보 기 클리어런스는 환자의 성별이 남자일 때 또는 헤마토크릿이 감소할수록 증가하였다. 그 외 파라미터는 다음과 같 이 계산되었다 Kα = 0.0787 (h-1); Q = 57.1 (L/kg/h); Vd-central compartment = 1,100 (L); Vd-peripheral compartment = 213,000 (L). 개체간 편차는 40% 미만이었으며, 개체내 편차를 포함하는 잔차는 24.02%였다. Conclusions: 사이클로스포린의 약동학적 특징과 그 클리어런스에 영향을 끼칠 수 있는 임상적 요인을 이해하는 것 은 환자 개개인의 용량과 용법의 결정 및 이상반응 발생의 예방에 유용할 수 있다. 한국인 조혈모세포이식환자에서 사이클로스포린의 약동학에 영향을 미치는 최종 파라미터를 구한 본 연구의 결과는 한국인 조혈모세포이식을 받은 성인환자에서 사이클로스포린의 모니터링 및 용량조절에 유용할 것으로 전망된다.

Aprepitant is a substance P/neurokinin-1 (NK1)-receptor antagonist that was approved in 2003 for prevention of CINV. In addition, updated anti-emetic guidelines that include the aprepitant regimen have been published by NCCN and ASCO. However there is scarce clinical data in Korea. The prospective study was performed to evaluate the prevention of high dose cisplatin induced nausea and vomiting in all patients who started high-dose cisplatin-based chemotherapy at our hospital. We checked the nausea severity and vomiting episodes by calling patients within 4 to 5 days after chemotherapy. The retrospective study was performed to compare the prevention of CINV in solid tumor patients who switched their anti-emesis regimen from the standard regimen to the aprepitant regimen. In aprepitant regimen, aprepitant was added to the same anti-emetic regimen used during previous cycles. We checked the nausea, vomiting grades and adverse events in electronic medical records (EMR). In prospective study, 195 patients were included in the analysis. 88.2% of patients achieved a complete response (no emesis and no rescue therapy). In retrospective study, 54 patients were reviewed. With aprepitant regimen, nausea and vomiting grades were improved in 22 patients (40.7%) and in 9 patients (16.7%), respectively. Compared with standard regimen, addition of aprepitant provided superior prevention against CINV in Korean patients receiving highly emetogenic cisplatin-based chemotherapy. Moreover, aprepitant significantly prevented CINV in patients who received the standard regimen to prevent CINV in previous chemotherapy cycles.

The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of nifedipine (6 mg/kg) after oral administration of nifedipine with or without atorvastatin (0.5 and 2.0 mg/kg) in rats, and also was to evaluate to the effect of atorvastatin on the CYP3A4 activity. The 50% inhibiting concentration (IC50) values of atorvastatin on CYP3A4 activity is 46.1 μM. Atorvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner. Coadministration of atorvastatin increased significantly (p<0.05, 2.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration (Cmax) of nifedipine compared to the control group. The relative bioavailability (RB%) of nifedipine was increased from 1.15- to 1.37-fold. Coadministration of atorvastatin did not significantly change the terminal half-life (T1/2) and the time to reach the peak concentration (Tmax) of nifedipine. 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. It might be suggested that atorvastatin altered disposition of nifedipine by inhibition of both the first-pass metabolism and P-glycoprotein efflux pump in the small intestine of rats. In conclusion, the presence of atorvastatin significantly enhanced the oral bioavailability of nifedipine, suggesting that concurrent use of atorvastatin with nifedipine should require close monitoring for potential drug interation.

This study was conducted to analyze cost-effectiveness of neoadjuvant chemotherapy for locally advanced head and neck cancer in Korean healthcare setting. We constructed a decision analytical model to estimate total costs and outcomes of paclitaxel+cisplatin (PC) or docetaxel+cisplatin+5-FU (DCF) for 2 years time horizon in 100 patient cohort with locally advanced head and neck cancer. Base analysis showed that cost savings of PC regimen were 379 million Korean Won and 231 million Korean Won in societal and payer's perspectives, respectively, compared to DCF regimen, and life saved was 0.18. PC regimen as a dominant strategy was found to be robust through sensitivity analyses.

Cefetamet pivoxil is a prodrug of cefetamet possessing a broad spectrum of activity against many aerobic gram-positive and -negative organisms. Although many literatures in abroad had introduced its pharmacokinetics about two decays ago, no data have been revealed in Korean subjects. Therefore, this study was aimed to investigate the pharmacokinetics of cefetamet following a single oral administration of cefetamet pivoxil in Korean healthy volunteers. After an overnight fast, a tablet of cefetamet pivoxil (500 mg) was given to eight volunteers, and blood samples were serially taken up to 12 h. Plasma concentrations of cefetamet were determined by HPLC with UV detection. Cefetamet reached the peak concentration (2.0±1.3 μg/ml) at 3.0±0.8 h, and mono-exponentially decayed at a half-life of 2.6±0.9 h. Three volunteers represented very low systemic exposure compared to the others, which provided very large interindividual variation in Cmax, and AUC. The present results were discussed and reviewed with the previously published data, and a couple of points are suggested for clinical trials of this drug in Korean subject including bioequivalence study.

Objective: This study aimed to develop information materials on vaccine's safety and adverse events which can be utilized by healthcare professionals when prescribing, dispensing and administering vaccines and also by non-healthcare professionals such as pharmaceutical distributors of vaccine. Methods: Information materials regarding vaccines from domestic and foreign governmental organizations, academies, medical organizations and pharmaceutical companies were reviewed. Advisory Committee which consisted of experts in the areas of the vaccine's safety verified the contents and the final information material. Results: Based on the collected data, we developed general guidelines including vaccine constituents, safety information and adverse events of each vaccines, storage and handling, and labeling information. The information materials were developed for both healthcare professionals and non-healthcare professionals such as vaccine distributors. Conclusion: Information materials on vaccine's safety and adverse events developed from this study could be utilized to provide useful information on the vaccine to the medical institutions and distributors.

주의력결핍 과잉행동장애는 미국에서 약 200만 명의 어린이에게 나타나는 심각한 만성 신경행동학적 장애이다. 주의 력결핍 과잉행동장애 치료의 중심은 약물요법이다. 그러나 현재 환자의 약 30%는 주의력결핍 과잉행동장애를 적응증 으로 갖도록 허가된 의약품들을 사용해도 적절한 치료효과를 얻지 못하고 있는 상황이다. Modafinil은 methylphenidate나 amphetamines와 같은 각성제와는 다른 약리학적 기전으로 중추신경계를 항진시킨다. 본 연구는 modafinil의 주의력결핍 과잉행동장애 치료효과에 대한 최신 지견을 얻고자, 1990년부터 2010년 3월까지 MEDLINE 에 등재된 논문을 ADHD와 Modafinil이라는 MeSH terms로 검색하여 추출한 자료 중에서 대조군이 사용된 무작위 배정 및 이중맹검 임상연구 사례만을 선별하여 임상적 유용성을 평가하였다. 현재 modafinil은 주의력결핍 과잉행동 장애 치료제로 허가된 의약품은 아니지만 최근 여러 국가에서 시행된 연구들은 modafinil이 안전하고 효과적인 주의 력결핍 과잉행동장애 치료제일 수 있다는 결과를 보여주고 있다.

The objective of this study was to find out guardians' understanding on the antibiotic use for their children under elementary school age. Survey analysis was performed on 671 questionnaire response sheets from the guardians for children (≤13 years old) attending daycare centers, kindergartens, or elementary schools located in eastern part and vicinity of Seoul, Korea. Result showed that majority of the guardians did not follow right direction for the use of antibiotic medications. About 80% of the guardians discontinued or reduced dosage of the antibiotic medications if symptoms relieved, and about 66% of them administered the drug always after meal although interval was not consistent. Furthermore, only one-fifth of the guardians understood right indication of antibiotic medications that it is of no use to take antibiotics for the treatment of common cold. About 65% of the guardians participated in this study responded that they received drug information for antibiotic medications from doctors or pharmacists. However, in terms of knowledge score regarding antibiotic drug use, their score was significantly lower than that of guardians who received the information from internet or mass media. This result suggests that patients counsel is not efficiently being practiced among healthcare professionals in the region surveyed in this study. Therefore, in conclusion, it appears that community pharmacists need to be more interactive in patients counsel when they dispense antibiotic medications.

Background: Clostridium difficile is the primary reason of the nosocomial diarrhea. The antimicrobial therapy plays a central role in the pathogenesis of Clostridium difficile associated diarrhea (CDAD). Although nearly all classes of antimicrobial agents have been associated with CDAD, clindamycin and the third-generation cephalosporins have traditionally been considered to the greatest risk factor. Recent studies have also implicated fluoroquinolones as high-risk agents due to increasing use of the agents. This study was to determine the incidence and the risk factors of CDAD related to the administered antibiotics and to assess the therapeutic regimen of metronidazole or vancomycin based on the C. difficile toxin assay Methods: A retrospective study was performed in patients with Clostridium difficile toxin assay at I Hospital (Incheon, South Korea) during the period from January 2007 through December 2007. Administrative, laboratory, and pharmacy data were collected from Electronic Medical Databases. Results: The analysis included 129 reported C.difficile toxin assay results, with 42 positive cases and 87 negative cases. Significant antibiotic risk factors for CDAD included the use of the fourth-generation cephalosporinse (OR=5.97, 95% CI 1.37-25.98, P=0.017). Administration of metronidazole was protective against CDAD (OR=0.30, 95% CI 0.12-0.74, P=0.009). Prolonged antimicrobial therapy has been associated with an increased risk of CDAD. The third-generation cephalosporins (OR=3.81, 95% CI 1.08-13.41, P=0.037) and aminoglycoside (OR=5.50, 95% CI 1.43-21.10, P=0.013) demonstrated greater risk for CDAD over 15 days than 8days or less days of treatment duration. Conclusions: The fourth and third generation cephalosporin, aminglycoside were the significant risk factors compared with other antibiotics, whereas metronidazole appears to be protective. The longer duration of antiobiotic use increased CDAD.

Recently, the prevalence of bladder cancer is increasing in the Korean society. As the risk factors of bladder carcinoma are variable, the early-stage diagnosis is regarded the best preventive practice. Hematuria is a specific sign of the malignancy as well as a kind of various medication-related adverse reactions. Some anti-coagulation therapy can cause bleedings including hematuria to the patients with cardiovascular diseases such as paroxysmal atrial fibrillation (PAF). Therefore, to the clinical pharmacists working in the anti-coagulation services (ACS), a closer monitoring of patients can give an opportunity to find certain ailments unexpectedly. In this case, a patient with PAF had episodes of sporadic hematuria in the course of warfarin therapy even though with its low levels of INR. An ACS pharmacist found a discrepancy between the bleeding symptoms and INR values, and recommended properly the patient to refer urologist. Fortunately, an early-stage of bladder carcinoma was found then followed by an excision performed to the lesion. Therefore, alert-minded and precise monitoring done by ACS pharmacist could optimize the therapeutic outcomes as well as increase the quality of life of the patient.