• 한국임상약학회지
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• 제13권1호
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• pp.1-4
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• 2003

Cyclosporine (CsA) has become well established as a potent immunosuppressive agent in the renal transplantation. However, therapy is complicated by large intraindividual and interindividual variability in pharmacokinetics of CsA and frequent undesirable clinical outcomes such as graft rejection and nephrotoxicity. The objective of this study was to determine the CsA trough blood concentrations that were associated with acute graft rejection and renal toxicity in renal transplant patients. Also, the ability of the current recommendation of therapeutic range for CsA to prevent graft rejections and CsA-associated renal toxicity was assessed. The clinical courses of the patients on CsA as an immusuppressive agent for preventing the graft rejection with renal ransplantation performed at Seoul National University Hospital from January 1995 to September 1998 were retrospectively reviewed. Total of 78 patients were included and three of them were retransplantation cases. Twenty-two acute episodes of rejection were identified, but only 16 episodes were clinically significant. Of these all the episodes occurred during the first month after transplantation except one. Mean daily doses of CsA were $427.2\pm72.1,\;352.6\pm56.8,\;308.62\pm48.3\;and\;268.47.1\;mg$ at posttransplant 1, 3, 6, and 12 months, respectively. Mean CsA whole blood though levels were $259.8\pm36.2,\;238.5\pm39,\;200.8\pm45.8\;and\;161.9\pm25.8\;ng/ml$ at posttransplant 1, 3, 6 and 12 months, respectively. Mean daily doses/weight were $7.9\pm1,\;6.4\pm1,\;5.3\pm0.7\;and\;4.6\pm0.7\;mg/kg$ at posttransplant 1, 3, 6 and 12 months, respectively. CsA doses decreased significantly as months progressed (p<0.001). During the first month after transplantation, only $12.5\%$ of the patients in rejection group had CsA concentration in therapeutic range, and 87.5, 93.8, and $100\%$ were within the therapeutic range at posttransplant 3, 6, and 12 months, respectively. These results suggested that CsA concentrations of $250\sim300\;ng/ml$ might be appropriate for preventing the acute rejection during the first posttransplant month.

• 한국임상약학회지
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• 제25권3호
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• pp.151-158
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• 2015

Objective: This study was designed to compare pegfilgrastim and filgrastim in diffuse large B-cell lymphoma (DLBCL) patients treated with a rituximab with cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP) regimen in terms of clinical efficacy and cost-effectiveness. Method: Clinical efficacy was measured by trough level of absolute neutrophil count (ANC), days of ANC under 50% of baseline value, days of ANC under 90% of baseline value, duration of ANC recovery to baseline value, days of ANC less than $0.5{\times}10^9cells/L$, and difference of peak and trough level of ANC during 1 cycle of R-CHOP regimen. To evaluate cost-effectiveness, total prices of used filgrastim and pegfilgrastim within 1 cycle of R-CHOP were analyzed. Results: In terms of clinical efficacy, trough level of ANC and days to ANC recovery showed statistical significance. The median trough levels of ANC with administration of filgrastim and pegfilgrastim were 0.18 and 1.94 (p = 0.021), respectively, and the median durations of ANC recovery to baseline value were 5.5 days and 2 days (p = 0.023), respectively. For the median days of ANC under 50% of baseline value, days of ANC under 90% of baseline value, days of ANC less than $0.5{\times}10^9cells/L$, and difference of peak and trough level of ANC during 1 cycle of R-CHOP, the pegfilgrastim group performed better than the filgrastim group. However the difference was not statistically significant. In terms of overall expense during 1 cycle of R-CHOP, pegfilgrastim is about 3.43 times more expensive than filgrastim. Conclusion: Pegfilgrastim is more efficient than filgrastim in terms of clinical efficacy. In terms of prices, pegfilgrastim is more expensive than filgrastim for patients, but it is more convenient in clinical use. Therefore, pegfilgrastim should be the preferred choice of G-CSF for neutropenic patients. Further comparative study of pegfilgrastim and filgrastim is needed.

• 한국임상약학회지
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• 제20권3호
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• pp.255-261
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• 2010

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, $Cefzil^{(R)}$ 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, $24.00{\pm}1.53$ years in age and $69.77{\pm}9.99$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ 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 $AUC_t$, $C_{max}$ and $T_{max}$ 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 $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Cefzil^{(R)}$ tablets, were -0.81%, -3.00% and -6.83% for $AUC_t$, $C_{max}$ and $T_{max}$, 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 $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Procezil tablet was bioequivalent to $Cefzil^{(R)}$ tablet.

• 한국임상약학회지
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• 제20권3호
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• pp.235-241
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• 2010

Bambuterol hydrochloride, dimethylcarbamic acid 5-[2-(1,1-dimethylethyl)amino-1-hydroxyethyl]-1,3-phenylene ester hydrochloride, is the prodrug of active ${\beta}_2$-adrenergic metabolite terbutaline. The purpose of the present study was to evaluate the bioequivalence of two bambuterol hydrochloride tablets, $Bambec^{(R)}$ 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, $23.86{\pm}1.65$ years in age and $68.98{\pm}9.58$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ 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 $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test with K-BE Test 2002 was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Bambec^{(R)}$, were -8.10%, -3.82% and 12.65% for $AUC_t$, $C_{max}$ and $T_{max}$, 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 $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Bambucol tablet 10 mg was bioequivalent to $Bambec^{(R)}$ tablet 10 mg.

• 한국임상약학회지
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• 제19권2호
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• pp.167-179
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• 2009

Hypertension is one of the most common chronic diseases and it causes cardiovascular and cerebrovascular disease. While antihypertensive drug use increased, it took 15% of national health insurance drug expenditure. This study aimed to examine the pattern of antihypertensive drug prescription using National Health Insurance claims database and compare it with recommendations of Korea Hypertension Treatment Guidelines. Among the antihypertensive drugs, calcium channel blocker(64.4%) was most commonly prescribed class, and diuretics(44.6%), angiotensin II receptor blocker(33.3%), angiotensin converting enzyme inhibitor(11.7%) was followed. Approximately 81% of antihypertensives prescription were without cardiovascular or cerebrovascular disease, and among the comorbid conditions, diabetes(10.7%) was most common. calcium channel blocker(62.3%) was mostly prescribed class for hypertension with angina pectoris, angiotensin receptor blocker(45.3%) with myocardial infarction, diuretics(70.2%) and calcium channel blocker(49.5%) with congestive heart failure. For Hypertension with cerebrovascular disease, calcium channel blocker(68.0%) and angiotensin receptor blocker(43.3%) were prescribed mainly. When it comes to diabetes, calcium channel blocker(57.2%) was still mostly prescribed and angiotensin receptor blocker(45.9%) followed. But in hospitals and tertiary hospitals, angiotensin receptor blocker(65.7, 66.1%) was mostly prescribed for the patients with diabetes. For Hypertension with chronic renal disease, angiotensin receptor blocker(59.5%), calcium channel blocker(56.5%), diuretics(54.6%) were mainly used. Average number of classes per prescribing was $1.89{\pm}0.89$ class, average days per prescribing was $33{\pm}19$ day. Among the hypertension without comorbidity, 40.5% of prescription was monotherapy and 58.8% of polytherapy included diuretics. Among the outpatient prescriptions, calcium channel blocker was the most commonly used class, and the prescription pattern in clinic did not closely followed recommendations of Hypertension Treatment Guidelines.

• 한국임상약학회지
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• 제26권4호
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• pp.306-311
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• 2016

Objective: This study was performed to compare the changes in the blood concentrations of tacrolimus when either itraconazole or voriconazole is together with tacrolimus to prevent or treat invasive aspergillus pneumonia (IAP) in patients with lung transplants. Therefore we can compare the degree of drug-drug interactions between tacrolimus and itraconazole against tacrolimus and voriconazole. Methods: Patients who were admitted and had lung transplants in a territory referral hospital from September 2012 to May 2015 were analyzed retrospectively. The effects of itraconazole and voriconazole on the plasma concentrations of tacrolimus were analyzed. Results: Mean tacrolimus concentrations was $10.49{\pm}2.35ng/mL$ vs. $10.95{\pm}2.98ng/mL$ (p=0.722), and mean concentration of tacrolimus over the dose of tacrolimus per day was $8.510{\pm}5.890(ng/mL)/(mg/d)$ vs. $15.45{\pm}28.47(ng/mL)/(mg/d)$ (p=0.947) in itraconazole vs. voriconazole group each. The ratio of the number of the results out of target tacrolimus concentrations to the total number of tacrolimus concentration results was $18.0{\pm}13.3%$ vs. $24.4{\pm}18.5%$ (p=0.185). Conclusion: There were no significant differences between itraconzaole and voriconazole to have influences on mean concentrations of tacrolimus over tacrolimus dose per weight per day. However voriconazole tended to raise tacrolimus plasma concentrations more than itraconazole. Safer and more effective drug management to prevent and treat fungal infections should be done by therapeutic drug monitoring not only of tacrolimus but of itraconazole and voriconazole in lung transplant patients.

• 한국임상약학회지
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• 제26권4호
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• pp.318-323
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• 2016

Background: Multidisciplinary team care (MTC) is a collaborative approach to treatment plan and ongoing care. We aimed to evaluate the clinical effect of MTC on the regulation of chronic kidney disease-mineral and bone disorder (CKD-MBD) complications in dialysis patients. Methods: This retrospective observational study was approved by the institutional review board. Among patients who have undergone dialysis at admission, the patients admitted to the nephrology ward were allocated to MTC group, and the others to usual care (UC) group. The MTC group had collaborative care by nephrologists, nurses, pharmacists, and nutritionists. The endpoints were the regulation of corrected calcium (cCa) and phosphate (P), the percent of patients in target level of cCa-P product ($cCa{\times}P$), and the prescription rate of non-calcium based P-binders. Results: A total of 163 patients were included from January to December 2009. A significant difference was shown in the percentage of patients in target $cCa{\times}P$ level at admission (MTC vs. UC, 81.40% vs. 91.67%; P = 0.038), but there was no significant difference at discharge. During admission, the cCa and P levels of patients in only UC group were significantly changed. In addition, compared with UC group, patients in MTC group were more likely prescribed appropriate P-binders, when they had higher $cCa{\times}P$ levels than $55mg^2/dL^2$ (P <0.001). Conclusion: It was found that MTC had beneficial effect on improving the regulation of CKD-MBD and the appropriate phosphate binder uses. Therefore, application of the MTC is anticipated to enhance quality of clinical care in chronic diseases.

• 한국임상약학회지
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• 제14권1호
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• pp.11-23
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• 2004

Although most children with idiopathic nephrotic syndrome respond to corticosteroid therapy, many responders show steroid dependency and frequent relapse. In these children, one of the major problems is the serious side effects resulting from continuous steroid therapy. Thus, this study was conducted to assess the therapeutic efficacy and safety of six-month cyclosporine treatment with the low-dose deflazacort therapy in children with nephrotic syndrome. Thirty children with steroid dependence (SD), frequent relapse (FR) and steroid resistance (SR) were enrolled in this study. They were treated with 6-month oral cyclosporine $(Cypol-N^{(R)})$ plus the low-dose deflazacort $(Calcort^{(R)})$ therapy at Samsung Medical Center from September 2002. The dosage of cyclosporine was started at 5 mg/kg/day and was monthly adjusted to maintain clinical remission and/or a trough blood level, while deflazacort dosage was reduced gradually. Clinical evaluation and monitoring of cyclosporine toxicity were performed every $2\sim4$ weeks. Outcomes were compared to the latest sir-month period of steroid only therapy before cyclosporine treatment. Student's t-test and ANOVA were used for statistical analysis. Out of 28 children with SD and FR, 23 $(82.1\%)$ sustained remission, and 5 $(17.9\%)$ experienced 1 or 2 relapses during therapy. Out of 2 children with SR, 1 child sustained remission, and 1 child showed no response. The mean duration of remission and occurrence of relapse were significantly improved (p <.0001). In addition, the mean dosage of steroid was significantly reduced (p=.003). Although a number of adverse effects occurred in this study, they were not so serious as to necessitate discontinuation of the therapy. No nephrotoxicity was observed. Twenty out of the 28 children who had been in remission relapsed after withdrawal of cyclosporine. Fifteen of these children showed relapse within a month. These results demonstrated that the combination of cyclosporine with the low-dose deflazacort was efficient and safe in children with SD and FR during the six-month treatment. However, further studies are necessary in order to resolve the problem of high relapse rate after discontinuation of cyclosporine.

• 한국임상약학회지
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• 제9권1호
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• pp.19-26
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• 1999

Adequate nutrition is important in maintaining optimal health. Malnutrition can expose individual to increased risks of morbidity and mortality. The purposes of this study were to determine the basal energy expenditure (BEE) of Korean healthy subjects and TPN patients using Bioelectrical Impedance Analysis (BIA) method and to compare these values with those predicted by Harris-Benedict equation (H-B). BEE values measured by BIA were compared with predicted BEE values by the H-B formula in 59 clinically stable TPN patients and 65 healthy volunteers. In healthy volunteers and TPN patients, statistically significant differences were not shown between the BEE values measured by BIA (1392.5 Kcal and 1325.9 Kcal) and those predicted by H-B formula (1384.1 Kcal and 1270.1 Kcal). In male volunteers, statistically significant differences were not shown between BEE values measured by BIA (1670.7 Kcal) and the H-B formula (1550.9 Kcal), but in female volunteers, statistically significant differences were shown between BEE values measured by BIA (1194.8 Kcal) and the H-B formula (1265.6 Kcal). In male TPN patients, statistically significant differences were shown between BEE values measured by BIA (1453.5 Kcal) and the H-B formula (1335.9 Kcal), but in female TPN patients, statistically significant differences were not shown between BEE values measured by BIA (1126.4 Kcal) and the H-B formula (1167.2 Kcal). In normal healthy volunteers, $90.8\%$ of BEE values measured by BIA and in TPN patients $89.8\%$ of BEE values measured by BIA were within $15\%$ of BEE values predicted by the H-B formula in non-obese subjects. In conclusion, BEE values predicted by H-B formula or measured by BIA can be applied to non-obese Koreans. However, these values should be confirmed with Indirect calorimetry for Koreans.

• 한국임상약학회지
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• 제17권1호
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• pp.13-18
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• 2007

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($C_{max}$)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.