Earticle

Purpose: Currently lung cancer ranks second in cancer for incidence rate and is a disease that ranks first for a deathrate by cancerous growth because it is already advanced at the time of diagnosis. The purpose of this paper was to ana-lyze the factors that affect the effectiveness of and rash occurrence by Epidermal Growth Factor Receptor TyrosineKinase Inhibitor (EGFR TKI) in patients with non-small cell lung cancer. Methods: A retrospective chart review of 100patients, who took EGFR TKI (erlotinib, gefitinib) among patients who were diagnosed with non-small cell lung can-cer in a Hospital in Korea between May 2005 and February 2008, was conducted. The drug effectiveness was evalu-ated by Response Evaluation Criteria In Solid Tumor. Results: EGFR mutation was the only factor associated with drugresponse (complete response and partial response). When stable disease was added to drug response as the evaluationparameter, ECOG and rash as well as EGFR mutation were found to be important factors. Survival, however, was notaffected by EGFR mutation. The factors influenced on survival were older age (≥65), low ECOG (1~2), adenocarci-noma and rash. In the case of rash, group with EGFR mutation or low ECOG showed significantly higher chance ofoccurrence. There was no significant difference in rash occurrence between gefitinib and erlotinib groups. Conclusions:Based on the results, EGFR mutation positive and low ECOG (1~2) were significantly important factors for both effec-tiveness of EGFR TKI and rash occurrence. Also, rash itself was found to be an independently significant factor for thedisease control and survival. Therefore, while administering EGFR TKI, patients who have the factors associated withrash occurrence should be closely monitored for effective and safe drug therapy.

In the recent, pharmacokinetic(PK)/pharmacodynamic(PD) modeling has appeared as a critical path tools in new drugdevelopment to optimize drug efficacy and safety. PK/PD modeling is the mathematical approaches of the relationshipsbetween PK and PD. This approach in new drug development can be estimated inaccessible PK and PD parameters,evaluated competing hypothesis, and predicted the response under new conditions. Additionally, PK/PD modeling pro-vides the information about systemic conditions for understanding the pharmacology and biology. These advantages ofPK/PD model development are to provide the early decision-making information in new drug development process, andto improve the prediction power for the success of clinical trials. The purpose of this review article is to summarize thePK/PD modeling process, and to provide the theoretical and practical information about widely used PK/PD models.This review also provides model schemes and the differential equations for the development of PK/PD model.

Hospital on-site preparations(HOP) have long been produced in most institutions since enactment of the Ministry ofHealth and Welfare Notification No. 92-12 in 1992. However, due to the unclear definition of the HOP, most institu-tions have trouble in production and reporting of the HOP. Therefore, in this study, the definition and range of HOP areexamined by questionnaire for 34 institutions, mainly teaching hospitals, which reported the items of HOP among 84institutions having 500 or more beds. It was found that 472 items and 1,116,888 jesu of the HOP were produced at 34institutions in 2006. Most institutions prepared 21~30 items of HOP, and the number of institutions producing5,000~10,000 forms was most prevalent. Accordingly, for HOPs whose need was identified by this study, pharmaceuti-cal companies should be pressed for commercialization.

The aim of this study was to evaluate the bioequivalence of two domperidone preparations. Bioequivalence assessmentwas conducted on 34 healthy volunteers who received two tablets (Domperidone Maleate, 12.72mg/tablet) in the fast-ing state, in a randomized balanced 2×2 cross-over study design. This whole study was performed according to theimplementation guidelines of the Korea Food Drug Administration. After dosing of two tablets, blood samples werecollected serially for a period of 36 hours. Plasma was analyzed for domperidone by using LC/MS/MS assay method.The analysis system was validated in specificity, accuracy, precision, and linearity. AUCt, (the area under the plasmaconcentration-time curve from the zero-time to 36 hr) was calculated through the trapezoidal rule. Cmax (maximumplasma drug concentration) and Tmax (time to reach Cmax) were compiled from the plasma domperidone concentration-time data of each volunteer. No significant sequence effect was found for the bioavailability parameters indicating thatthe cross-over design was properly performed. The 90%-Confidence intervals of the AUCt ratio and the Cmax were fromlog 0.8007 to log 1.1240 and log 0.8645- log 1.2483, respectively. These values were within the acceptable bioequiva-lence intervals between 0.80 and 1.25. Therefore, this study demonstrated that two formulations have bioequivalencewith respect to the rate and extent of absorption.

Alendronate is a bisphosphonate that selectively inhibits osteoclast-mediated bone resorption. Dosing convenience is animportant element for the enhancement of patient compliance and the effective management of osteoporosis. The pur-pose of this study was to compare the effectiveness and compliance among alendronate pharmaceutical products(oralonce-weekly alendronate 70mg, daily alendronate 10mg, and once-weekly alendronate 70mg with Vitamin D3 2800IU) in terms of the change in bone mineral density (BMD), biochemical markers, and compliance estimates. A retro-spective chart review was conducted in patients with osteoporosis who received alendronate 70mg (Group 1), alendr-onate 10 mg (Group 2), or alendronate 70mg with Vitamin D3 2800 IU (Group 3) at the endocrinology department ofa hospital in Korea from Jan. 1, 1998 to Mar. 31, 2008. The primary endpoints were the increases in spine antero-pos-terior BMD T-score and femur trochanter BMD T-score, and the compliance of alendronate products. Secondary end-points included changes in bone turnover-related biochemical markers including bone-specific alkaline phosphatase,urinary N-terminal telopeptides (NTX) and osteocalcin, and in serum vitamin D3 concentration. There was no statisticaldifference in the BMD increase among the three alendronate products; spine BMD T-score increased by 0.49±0.52,0.39±0.48 and 0.50±0.41, and femur trochanter BMD T-score by 0.29±0.42, 0.21±0.53 and 0.24±0.22 in Group 1, 2 and3, respectively. With respect to the increases in femur trochanter BMD T-score and the decreases in NTX and osteocal-cin, 70mg once-weekly group was remarkably superior to 10mg daily group (p<0.05) The compliance of 70mgonce-weekly group was significantly higher than that of 10mg daily treatment group (p<0.001). In conclusion, allthree alendronate treatment groups were equivalent in effectiveness, and the compliance of 70 mg once-weekly groupwas better than that of 10 mg daily treatment group.

The purpose of this study was to investigate the effect of naringin, one of flavonoids, on the pharmacokinetics and bio-availability of nimodipine in rabbits. Pharmacokinetic parameters of nimodipine were determined in rabbits after oraladministration of nimodipine (16mg/kg) with or without naringin (1, 5 or 15mg/kg). Nimodipine was analyzed byhigh performance liquid chromatography using Hypersil ODS column. Naringin significantly (p<0.05) increased the areaunder the plasma concentration-time curve (AUC) and the peak concentration (Cmax) of nimodipine at 5 and 15mg/kg.The absolute bioavailability (AB%) of nimodipine by prescence of naringin (5 or 15mg/kg) increased from 32.2-36.9%(p<0.05) compared to the control (22.0%). However, presence of naringin had no significant effect on the eliminationrate constant (Kel) of nimodipine. There were no apparent changes of the time of peak concentration (Tmax) of nimo-dipine by coadministration. These results suggest that the increased bioavailability and the significant changes of thesepharmacokinetic parameters of nimodipine by naringin may be attributed to the potential of narigin to inhibit cyto-chrome P450 (CYP) 3A4 and P-glycoprotein efflux pump in the liver and intestinal mucosa.

The impacts of guideline for digestives on physicians' prescription of GI medication Clinical practice guidelines pro-vide benefits to physicians, patients, and researchers. It also helps doctors to make decisions in medical services. Inmany countries, practice guidelines lead to activities of quality improvement and are developed using evidence basedmethods. This research was to assess the impacts of Korean Medical Association's guideline for digestives on thechange of physicians' behavior. This study was progressed as one-group pre-test post-test quasi-experimental designusing health insurance claims data. The unit of analysis was institution. Data was analyzed using paired t-test forchange of prescription rate before and after the distribution of practice guidelines. And the multiple regression analy-sis was performed to examine the independent impact of the guideline on the prescribing rate of GI medication. Pre-scription rates of GI medication per claim by medical institution increased significantly, 1.98%point(from 50.27% to52.25%) and multivariate regression analysis showed significant increase in the prescription rate of GI medicationafter the distribution of guideline(p<0.001). In conclusion, the distribution of guideline for digestive might not havethe effects on the change in provider's behavior. Furthermore, to activate the use of practice guideline, it would benecessary to educate the contents to physicians as well as to develop practice guideline.

생물학적동등성시험기준에 따라 플레록사신정 (Fleroxacin, 100mg) 을 시험약으로 하고 메가로신정 100mg을 대조약으로 하여 2×2 교차 시험법에 따라 건강한 성인 지원자 24명에게 3정 (fleroxacine, 300mg/정) 씩을 경구투여한후, 각 피험자들의 혈중 약물농도 데이터로부터 구한 혈중농도-시간곡선하면적(AUCtmax.) 과 최고혈중농도 (Cmax)등의 생체이용률 파라미터에 대해 통계학적으로 고찰하여 두 제제간의 생물학적동등성을 평가하였다. 혈중 약물농도는HPLC/UV 검출기로 분석하다. 플레록사신정의 대조약과 시험약에 대한 동등성 여부를 종합적으로 판단하여 보면 생물학적동등성시험의 판단 기준인 2항목 (AUCt, Cmax) 에 대하여 두 가지 비교항목 중 AUCt 값의 경우 대조약은44.26±7.12µg·hr/mL, 시험약은 4.11±1.63µg/mL이며 두 약물의 로그변환한 평균치 차의 90% 신뢰구간은 log0.9570 에서 log 1.0565 이다. Cmax 값의 경우 대조약은 45.16±10.04µg·hr /mL, 시험약은 3.78±1.01µg/mL 이며, 대조약과 시험약의 로그변환한 평균치 차의 90% 신뢰구간이 log 0.8369에서 log 1.0626 로서, AUCt 와Cmax 두 항목 모두 log 0.8 에서 log 1.25 이내이어야 한다는 생물학적동등성시험 기준을 충족시켰다. 이러한 결과들로부터, 시험약 플레록사신정 (Fleroxacin, 100mg)은 대조약인 메가로신정 100mg 에 대하여 생물학적동등성의 판단 기준인 두 항목 AUCt와 Cmax에 있어서 생물학적으로 동등함을 알 수 있었다.