Earticle

Methotrexate(MTX)는 소아 골육종 환자에서 의 고용량을 사용하고 있다. 현재, 소아 골육종 환자에서 신기 능에 따른 고용량 MTX의 임상 약동학은 연구되어 있지 않다. 따라서 본 연구에서는 신기능에 따른 MTX 약동학을 이용하여 구내염을 최소화하는 방법을 제시하고자 하였다. 방법: 환자들의 의무기록지를 후향적 방법으로 검토하였다. 한 병원에서 골육종으로 진단받고, 치료 받은 환자들을 대상으로 정상 신기능군과 비정상 신기능군으로 나누었다. 두 군에 MTX 투여 후 혈중 농도를 각각 비교하였고, 최고 혈중농도도 비교하였다. 혈중 농도와 구내염의 관련성, CL, AUC와 구내염의 상관관계를 분석하였다. 각 군의 terminal half-life, CL, Vss의 평균과 mea residence time(MRT)의 평균을 구하였고, 두 군간 각각을 비교하였다 . 결과: 환자는 6명이었고, 평가 가능한 총 MTX 투여 회수는 34회였다. MTX 투여 후 최고혈중 농도, 24,48 시간의 혈중농도는 통계적으로 유의성 있는 차이가 있었고, 72,96 시간에서의 농도는 두 군간 유의성이 없었다. 각 군에서 혈중농도와 구내염의 상관관계, 그리고 CL, AUC와 구내염의 상관관계는 발견되지 않았다. Vss를 제외한 모든 파라미터들(terminal half-life, CL, MRT)은 통계적으로 유의성 있는 차이가 있었다. 결론: 비정상 신기능 군에서 MTX 투여 시작 후 24, 48 시간에서의 혈중농도가 더 높고, 변동이 심했다. 또한 MTX의 CL는 감소했고, 혈중농도는 증가하였다. 이러한 사실로 MTX 투여 전 후 혈중 크레아티닌이나 또는 크레아티닌 청소율 모니터링이 필요하다는 것을 알 수 있으며, MTX 투여가 끝난 직후 그리고 그 이후 24 시간 간격으로 혈중 농도를 측정해야함을 알 수 있다.

Purpose: To determine the short (1 year of transplant) and long-term (1-5 years of transplantation) risk factors affecting the graft and patient survival in kidney transplantation recipients. Methods: Records of 149 patients who received kidney transplantation in 1996 from Asan Medical Center were followed for 5 years retrospectively. Results: All patients initiated triple immunosuppressive therapy with cyclosporine, prednisone and azathioprine. One, two, three, four, five year patient and graft survival rates were 98.7%, 98.0%, 98.0%, 97.3%, 97.3%, and 96.6%, 95.2%, 94.6%, 92.5%, 91.8%, respectively. There were 30 cases of acute rejection (AR) and 6 cases of chronic rejection (CR) within months and months of transplantation, respectively. The risk factors for AR were donor's age older than 30 years (p=0.02) and cardiovascular disease (p=0.05). The risk factors for CR were AR (p=0.0169) and episode of complications (p=0.0330). Increasing period of dialysis (p=0.0473), episodes of AR (p<0.0001) and complication (p=0.0317) were significant factors for graft loss. Seven grafts were lost from noncompliance during 1-5 year period. The most com- mon cause of the graft loss for both periods was the graft rejection. The graft survival rate was significantly lower in patients with than without rejection episodes (77.4% vs. 90.0%, p=0.002). Conclusions: Survival rate of the graft with rejection was significantly lower. The risk factors affecting AR were donor's age older than 30years and CVD. AR and episode of complications within 1year were the risk factors for CR and graft loss.

Doxorubicin (DXR) is a type of anti-cancer drug called an 'anthracycline glycoside', It works by impairing DNA synthesis, a crucial feature of cell division, and thus is able to target rapidly dividing cells. Doxorubicin is a very serious anti-cancer medication with definite potential to do great harm as well as great good. A liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method was developed to identify and quantify DXR in small-volume biological samples. After the addition of internal standard (IS, daunorubicin methanol solution) into the serum sample, the drug and IS were extracted by methanol. Following vortex for a 1min and centrifugation at 15,000g for 10 min the organic phase was transferred and evaporated under a vacuum. The residue was reconstituted with of mobile phase and was injected into C18 column with mobile phase composed of 0.05M ammonium acetate (0.1 M acetic acid adjusted to pH 3.5) and acetonitrile (40:60, v/v). The flow rate was kept constant at . The ions were quantified in the multiple reaction mode (MRM), using positive ions, on a triple quadrupole mass spectrometer. The lower limits of quantification for Doxorubicin in plasma and small tissues were approximately 0.5 ng/mL and 0.5 ng/mL respectively. Intra- and inter-assay accuracy (% of nominal concentration) and precision (% CV) for all analytes were within 15%, respectively.

The stability of cefditoren in three kinds of oral liquid preparations at 4 and was studied for 90 days. Two tablets of 100 mg cefditoren pivoxil were mixed with 200 mL of each oral liquid syrup, which is Pebron syrup (oxolamine citrate 10 mg/mL), syrup (ambroxol hydrochloride 3 mg/mL) or suspension (acetaminophen encapsulated 32 mg/mL). Three samples of each formulation were refrigerated and three were stored at room temperature . At predetermined time, samples were assayed by stability-indicating HPLC method. The chromatographic analysis after deliberate degradation showed no evidence of any breakdown product likely to interfere with the chromatographic peak of the parent substance. The relation between cefditoren pivoxil concentration and peak area was linear from 10 to . The analysis method was precise, with coefficients of variation no greater than 3.6%. Cefditoren was stable in syrup up to 4 weeks regardless of the temperature; in suspension and Pebron syrup, it was stable for at least 28 and 45 days, and 7 and 45 days at 25 and , respectively. The percentages of initial cefditoren concentration remaining after 90 days were in syrup, suspension and syrup at 25 and , respectively. The pH variations of all test solutions were minimal, which was within 0.5. The results indicated that the stability of cefditoren was significantly affected by liquid solutions mixed with cefditoren, and storage tempertature.

Fexofenadine, one of selective histamine receptor antagonists, has been used for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. The bioequivalence of two fexofenadine hydrochloride preparations, containing 120 mg fexofenadine hydrochloride, was evaluated according to the guidelines of Korea Food & Drug Administration(KFDA). The test product was Hanmi Fexofenadine Hydrochloride Tablet made by Hanmi Pharm. Co. and the reference product was Allegra Tablet made by Handok Parmaceuticals Co.. Twenty healthy male subjects were randomly divided into two groups and a cross-over study was employed. After one tablet was orally administered, blood was taken at predetermined time intervals and the concentration of fexofenadine in plasma was determined using a validated HPLC method with fluorescence detector. Two pharmacokinetic parameters, , were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of were log 1.149 and log 1.109, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Hanmi Fexofenadine Hydrochloride Tablet 120 mg is bioequivalent to Allegra Tablet 120 mg.

In clinical trials, it is important to have well designed case report forms (CRF) in order to obtain good quality of data. If CRF design at the first stage of your study goes wrong, after all efforts have been made, you may find practical difficulties in data analysis at the final stage of your study because of incomplete or wrong information. In this paper, the following rules fundamental to CRF design are introduced: rules in general, rules of format or style, categorized responses, forms with multiple records per subject, and international studies. Investigators are well aware of research goals, however sometimes they do not know how to express it on CRF. If they understand the rules fundamental to CRF design, time for CRF development will be saved and CRF completeness will be enhanced.

Dyslipidemia is an important CHD risk factor in diabetic patients. We conducted this study to assess the pattern of dyslipidemia in type 2 diabetes patients, to examine the demographic and clinical factors associated with dyslipidemia and to evaluate attaining within the lipid target goals and treatment strategies. A retrospective analysis was conducted among patents diagnosed type 2 diabetes at outpatient clinic in endocrinology between January 2003 and December 2004. Clinical history and physical examination were reviewed and laboratory data including blood glucose, HbAlc, lipid levels were recorded sequentially at least 1 year. In 882 patients with type 2 diabetes, 437 patients (49.6%) have dyslipidemia and 73% of them (319 patients) received lipid-lowering agents. 244 patients (94 males, 150 females, mean age 60 years old) were susceptible to analyses. The most frequent pattern of dyslipidemia is high LDL level and high TG levels (28%). Metabolic syndrome and macrovascular complication were significant negative independent association with lipid levels within the target goals (p<0.05). Only 15.2% (19 males, 18 females) attained within the lipid tar- get goals. Patients with diabetic dyslipidemia need maximization of lipid-lowering agents, increasing the fibric acid derivatives prescription and the effort to correction of low HDL and/or high TG.

Aceclofenac, a nonsteroidal antiinflammatory agent of a phenylacetic acid type, has been used for rheumatoid arthritis and osteoarthrits. Although the metabolic pathway of aceclofenc is relatively well-known in vitro, pharmacokinetic profiles of its three major or metabolites are still unclear in human. The present study was designed to investigate pharmacokinetic profiles of the metabolites of aceclofenac, and to evaluate the bioequivalence of the generic preparation of aceclofenac 100 mg tablet. Blood samples were serially collected for a period of 12 hours following a single oral administration of 100 mg aceclofenac in 20 healthy human volunteers. A simple protein precipitation with acetonitrile was employed to purify those substances from plasma. Aceclofenac, diclofenac, 4'-hydroxyaceclofenac and 4'-hydroxy-diclofenac in heparinized plasma were simultaneously measured with flufenamic acid, an internal standard, using HPLC coupled to a tandem mass spectrometer. Time courses of 4'-hydroxydiclofenac, diclofenac and aceclofenac plasma concentrations were clearly revealed, and the pharmacokinetic properties were analyzed. The 90% confidence intervals for the ratios of test/reference for log-transformed AUC and lie within 0.80-1.25.

The purpose of this study was to investigate the effect of naringenin, one of flavonoids, on the pharmacokinetics and bioavailability of diltiazem (15 mg/kg) after oral administration of diltiazem with or without naringenin (2.0, 10 and 20 mg/kg) in rabbits. Coadministration of naringenin increased the absorption rate constant , the area under the plasma concentration-time curve (AUC) and peak concentration of diltiazem compared to the control group, but only significantly (p<0.05) by 10mg/kg of naringenin coadministration. The absolute bioavailability (AB%) of diltiazem by coadministration ranges from 7.8% to 10.3%, increased more than control (7.2%), and relative bioavailability (RB%) of diltiazem is increased from 1.08- to 1.43-fold. Coadministration caused on significant changes in the terminal half-lives and the time to reach the peak concentration of diltiazem. On the other hand, coadministration of naringenin increased the AUC desacetyldiltiazem, significantly at the dose of 10mg/kg. But the metabolite ratio (MR) was decreased, significantly at 10mg/kg of naringenin. Based on these results, we can make a conclusion that the increased bioavailability and the significant changes of these pharmacokinetic parameters might be due to naringenin, which possess the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein efflux pump in the intestinal mucosa

Gabapentin, 1-(aminomethyl-1-cyclohexyl)acetic acid, is anew antiepileptic drug related to acid(GABA) currently being introduced in therapy worldwide. The bioavailability and pharmacokinetics of gabapentin capsules were examined in 22 volunteers who received a single oral dose in the fasting state by randomized balanced crossover design. After dosing, blood samples were collected for a period of 24 hours and analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Time course of plasma gabapentin concentration was analyzed with non-compartmental and compartmental approaches. , the kinetic computer program, was used for compartmental analysis. One compartment model with first-order input, first-order output with no lag time and weighting by was chosen as the most appropriate pharmacokinetic model for the volunteers. The major pharmacokinetic parameters and other parameters of (test drug) and (reference drug) were estimated by non-compartmental analysis and compartmental analysis. The 90% confidence intervals of mean difference of logarithmic transformed were , respectively. It shows that the bioavailability of the test drug is equivalent with that of the reference drug. There was no statistically significant difference between the two drugs in all pharmacokinetic parameters.

날트렉손은 수용체에 특이적이고 선택적으로 길항작용을 나타내어 마약이나 마약성 진통제의 강한 의존성 치료에 쓰일 뿐만 아니라, 알코올 의존성 치료에도 쓰이는 약물이다. 본 연구는 날트렉손 제제인 레비아 정 (50 mg tablet, 제일약품) 을 대조약으로 하여 시험약인 명인 제약의 트락손 50 mg정의 생물학적 동등성 평가를 하기 위해 22명의 건강한 지원자를 모집하였다. 지원자를 두 군으로 나누어 1정씩 투여하였고 교차시험을 실시하였다. 날트렉손의 혈장 중의 농도를 정량하기 위하여 발리데이션된 LC/MS/MS를 사용하였다. 채혈 시간은 투약 전 및 투약 후 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12 시간에 걸쳐 시행하였다. 생물학적 동등성을 판정하기 위한 파라미터로 12시간까지의 혈장 중 농도 곡선 하 면적과 최고 혈중 농도 를 사용하였다. 의 평균은 (시험약)과 (대조약) 으로 관찰되었고, 의 경우 각각 12.01 ng/m1 (시험약)과 12.27 ng/ml (대조약)으로 관찰되었다. 의 경우 로그변환 한 평균치 차의 90%의 신뢰구간이 log0.95-log1.07이었고, 의 경우 log0.87-log1.14로 계산되어 두 항목 모두 log0.8-log1.25이어야 한다는 식품의약품 안전청과 FDA의 기준을 모두 만족시켰다. 이상의 결과를 종합하면 시험약 트락손 정 50mg 은 대조약 레비아 정 50 mg에 대하여 생물학적으로 동등한 것으로 판정되었다.