Interest in equivalence trials has been increasing for many years because ethical requirements preclude the use of a placebo. Equivalence trials aim to show that two treatments have equivalent therapeutic effects. The design of a clinical trial to test the equivalence of two treatments differs from that of testing efficacy. The conventional null hypothesis of no difference between two treatments is not appropriate for equivalence trials. So, we must use non-zero (inequivalence) null hypothesis to test clinical equivalence between two treatments. It's very important but difficult to specify a threshold value $({\delta})$ which is clinically insignificant in advance for defining equivalence. Statistical analysis should be based on confidence intervals. When we have predefined a range of equivalence, we can check whether the confidence interval obtained on the observed difference lies entirely within the range. If it does, equivalence is demonstrated. In this paper, the several issues of equivalence clinical trials are discussed: choice of equivalence margin, testing statistical hypothesis, and estimating confidence intervals.

Background: Intradialytic hypotension is a disabling complication in end-stage renal disease(ESRD) and has a multifactorial etiology. Autonomic dysfunction occurs in up to 50% of patients with end-stage renal disease(ESRD) and plays a key role in intradialytic hypotension in some patients. Sertralin hydrochloride, a central nervous system serotonin reuptake inhibitors, has been shown to be an effective treatment of hypotension caused by autonomic dysfunction. Aim of this study is to determine whether sertralin is effective in ameliorating intradialytic hypotension. Methods: This study was prospective that included 7 consecutive patients who had intradialytic hypotension. The data from 4-week pre-sertralin period were compared with the data from a 4 week sertralin period. The patients were given a 50 mg of sertralin 30 minutes before each hemodialysis session. Results : There was a statistically significant improvement in lowest intradialytic systolic blood pressure (from $115.4{\pm}22.6$ to $124.1{\pm}20.7$ mmHg, P=0.003), lowest intradialytic dialstolic blood pressure ( from $68.8{\pm}14.9$ to $72.9{\pm}11.8$ 11.8 mmHg, P=0.02), lowest intradialytic mean arterial pressure( from $83.3{\pm}17.1$ to $89.3{\pm}13.8$ mmHg, P=0.004), post-hemodialysis systolic pressure(from $142.1{\pm}22.5$ to $149.5{\pm}22.1$ mmHg P=0.007), post-hemodialysis diastolic pressure(from $79.3{\pm}10.7$ to $83.2{\pm}9.6$ mmHg, P=0.002), post-hemodialysis mean arterial pressure(from $100.3{\pm}13.3$ to $105.3{\pm}12.4$ mmHg, P=O.OO1) during sertralin period. In addition, the number of symptomatic hypotensive episodes per dialysis session during the sertralin period significantly was lower than that during the pre-sertralin period( mean $0.45{\pm}0.5$ episodes per session vs $0.13{\pm}0.3$ episodes per session; P<0.05). Conclusions: It is concluded that the short-term (4 weeks) use of sertralin hydrochloride reduces intradialytic hypotension in ESRD patients.

Objective: To assess the factors affecting the free fraction of phenytoin in serum and the per formance of currently available equations used to predict normalized total phenytoin concentrations in Korean patients and to identify the most appropriate equation for Korean patients. Design : Patients with both total and free phenytoin concentrations measured were enrolled by a retrospective chart review. Setting : Samsung Medical Center in Seoul, Korea; a 1400-bed university teaching hospital. Participants : Total of 227 inpatients or outpatients were enrolled: 196 patients with norma albuminemia and 31 with hypoalbuminemia. Patients receiving drugs known to displace phenytoin or those with renal failure or abnormal liver enzymes were excluded in evaluating the performance of the equations (n = 115). Main outcome measures: Correlation between free fraction of phenytoin and factors such as age, sex, serum albumin, BUN, Scr, AST, ALT and concurrent medications was assessed by multiple regression analysis. Predictive performance of the equations was evaluated using bias (MPE ; mean prediction error) and precision (RMSE ; root mean squared error), the methods proposed by Sheiner and Beal. Results : Free fraction of phenytoin correlated well with all factors ($r^{2}$=0.51). However, only albumin and concurrent medication showed statistically significant correlation(p<0.05). Normoal buminemia patients exhibited a weak correlation ($r^{2}$=0.16) and hypoalbuminemia patients exhibited a strong correlation ($r^{2}$=0.69) between free fraction of phenytoin and the factors. Albumin and concur rent medication were shown to be the significant factors in these subgroups as well. The age especial ly had shown a significant correlation with free fraction of phenytoin in hypoalbuminemia patients. Bias (MPE) and precision (RMSE) of the equations of predicting normalized total phenytoin concentrations were as follows: the Sheiner-Tozer equation (MPE=2.1, RMSE=5.82), the revised Winter Tozer equation (MPE=-0.74, RMSE=5.09), the new equation using the affinity constant of 0.24 (MPE=-0.26, RMSE=5.07). Conclusions: There was a high correlation between free fraction of phenytoin and the factors affecting protein binding such as albumin and concurrent medication. In addition, the age was found to have a significant impact on free fraction of phenytoin in hypoalbuminemia patients. The affinity constant of 0.24 had smaller bias than 0.20 or 0.25 in Korean patients. However, it needs to be reassessed in a larger study with Korean patients.

본 논문은 항생제 사용으로 인한 약제비 부담과 건강상의 피해가 사회문제화 되고 있는 시점에서 항생제 적정 사용 정책 개발에 필요한 제반 자료를 제공할 목적으로 항생제 사용량 및 약제비를 산출하고 의료기관별, 제형별, 성분군별 항생제 사용량과 약제비를 비교 분석하였다. 본 연구에서는 IMS data의 사입자료를 이용하여 항생제 사용량과 약제비를 분석하였다. 항생제 사용량은 국제적으로 통용되는 지표인 DDD(the defined daily dose) 방식을 적용하여 산출하였으며, 항생제 약제비는 IMS data에 나타난 가격을 최종소비자 가격으로 보정한 후 구하였다. 주요 연구결과는 다음과 같다. 첫째, 항생제 약제비는 1998년을 기준으로 할 때 그 규모가 1조원대에 이르며 연평균 11.5% 정도 지속적으로 증가하는 양상을 보이고 있어 항생제 사용으로 인한 비용부담이 큰 것을 알 수 있다. 둘째, DDD를 적용하여 항생제 사용량 산출을 시도하였는데 그 결과 1997년의 경우 33.2 (DDD/1,000명/1일)로 현재 OECD에 보고된 국가와 비교할 때 가장 높은 것으로 나타났다. 항생제 사용량은 항생제 내성과 밀접한 관련이 있음을 고려한다면 현재의 높은 내성수준은 과다한 항생제 사용의 결과로 볼 수 있다. 특히 내성율이 세계 최고 수준인 것으로 알려진 penicillin의 사용량은 17.1에 달하였다. 셋째, 항생제 약제비 및 일일사용량 기준단위(DDD)를 적용한 항생제 사용량에 대한 비교분석을 실시한 결과 항생제 약제비와 항생제 사용량은 제형별, 성분별, 기관별로 정반대의 양상을 보이는 것으로 나타났다. 일일 사용량 기준단위(DDD)에 의한 항생제 소비량은 제형별로 볼 때 경구제가 30.65로 주사제 2.52보다 월등히 많은 것으로 나타났으나 약제비 구성비는 경구제가 43.9%, 주사제가 56.1%로서 주사제가 더 높았다. 또한 성분별로 볼때도 비슷한 경향이 나타났는데 항생제 약제비 비중이 가장 높았던 cephalosporin계 (46.0%)의 의약품 사용량은 97년 2.2로서 기준단위 사용량(DDD)으로 볼 때는 사용량이 penicillin계(17.1DDD/1,000명/1일)의 약 1/8 정도에 불과한 것으로 나타났다. 그리고 penicillin계는 약제비중 18. % 정도로서 전반적으로 감소하는 경향을 보이는 성분군이었으나 사용량은 17.13으로 전체의 51.6%를 차지하였다. 이러한 결과는 경구, 주사와 항생제 성분별로 가격차가 매우 많다는 것을 의미하는 것이다. 실제 의료보험약가 기준액표에 등재된 가격으로 cephalosporin계와 penicillin계를 비교한 결과 cephalosporin계 항생제는 $403{\sim}20,522$원으로 고가인 반면 penicillin계 항생제는 75원${\sim}1,960$원으로 상대적으로 저렴한 가격대를 구성하고 있었다. 또한 주사제와 경구제의 가격차를 보면 통일한 항생제 분류군내어서 주사제와 경구제의 가격차이는 최고 37.4배까지 이르렀다. 넷째, 약국을 포함한 의료기관별로 볼 때 항생제 약제비는 병원(64.5%), 의원(18.0%), 약국(17.4%)의 순으로 나타났으나 사용량은 약국 16.2, 의원 14. 2, 병원 2.8(DDD/1,000명/1일)로서 반대되는 경향 을 보였다. 이는 항생제 사용은 양으로 볼 때 약국 및 의원에서 집중적으로 이루어지고 있으나, 주로 상대적으로 저렴한 경구제 및 penicillin, tetracycline계 항생제를 많이 사용하는데 비해 병원에서는 상대적으로 고가인 주사제 및 cephalosporin계 주사제를 많이 사용한 결과로 볼 수 있다. 따라서 항생제 관리정책을 시행할 경우, 약국 및 의원은 주로 감기 같은 흔한 상병을 중심으로 항생제 사용량이나 기간 및 사용적합성 측면을 중심으로 관리가 이루어져야 하고, 병원의 경우는 비용적 측면에서 고가항생제 사용에 대한 관리정책이 실시되어야 할 것이다.

연구배경 : 사람 flavin-containing monooxygenase 3(FMO3)의 활성도를 비관혈적으로 측정하기 위해 trimethylamine (TMA)이 이용될 수 있으나 TMA는 많은 식이중에 존재하여 활성도 측정에 어려움이 있어, 본 연구진은 최근에 생체내 FMO 활성도를 측정하기 위한 비관헐적 ranitidine N-산화대사능 검사를 개발하였다. 본 연구에서는 생체내 TMA N-산화대사능과 ranitidine N-산화대사능에 미치는 FMO3 $E_{158}K$K 및 $E_{308}G$ 돌연변이의 효과를 교차시험으로 조사함으로써. FMO3 유전자형에 대한 두 가지 FMO 표현형 검색방법의 민감도를 비교하였다. 방 법 : FMO3 유전자의 $K_{158}$ 및 $G_{308}$ 돌연변이에 대해 유전자형 검색을 시행한 36명의 건강한 한국인 자원자에서 TMA N-산화대사능과 ranitidine N-산화대사능을 이용하여 FMO 활성도를 측정하였다. TMA N-산화대사능은 24시간 소변중의 TMA n-oxide(TMAO)와 total TMA(TTMA)의 비로 측정하였으며, ranitidine N-산화대사능은 150 mg ranitidine을 경구투약후 8시간까지 배설된 소변중의 ranitidine N-oxide와 ranitidine의 비로 측정하였다. 결 과 : TMAO/TTMA 비에 대해서는$K_{158}$ 돌연변이 대립형질에 대해 동형접합자이거나 이형접합자인 13명이 wild type $E_{158}$ 대립형질에 대해 동형접합자인 23명과 유의한 차이가 없었으며$G_{308}$ 돌연변이 대립형질에 대해 동형접합자이거나 이형접합자인 12명이 wild type $E_{308}$ 대립형질에 대해 동형접합자인 24명과 유의한 차이가 없었다. 그러나, ranitidine N-oxide/ranitidine 비에 대해서는, $K_{158}$ 돌연변이 대립형질에 대해 동형접합자이거나 이형접합자인 13명이 $E_{158}$ wild type 대립형질에 대해 동형접합자인 23명에 비해, 그리고 $G_{308}$ 돌연변이 대립형질에 대해 동형접합자이거나 이형접합자인 12명이 $E_{308}$ wild type 대립형질에 대해 동형접합자인 24명에 비해 각각 통계적으로 유의하게 낮았다. 결 론 : 한국인 FMO3 유전자에서 흔하게 발견되는 두 가지 돌연변이인 $E_{158}K$ and $E_{308}G$ 유전자형은 TMA N-산화대사능과는 상관관계가 없었으나 ranitidine N-산화대사능으로 측정한 FMO 활성도와는 통계적으로 유의한 상관관계를 나타내었다.

연구배경 : TPMT 효소는 여러 인종에서 유전적 다형성이 있으며 백혈병 환자에서 azathioprine 치료시 TPMT 활성이 낮은 경우 활성 대사물인 6-TGN의 독성이 증가되었다. 본 연구에서는 azathioprine으로 면역억제요법올 시행하는 신장이식환자에서 TPMT 활성의 다형성에 따라 6-TGN의 농도 및 치료 효과에 영향을 미치는지를 연구하고자 하였다. 방 법 : 신장이식 후 triple therapy를 시행하는 41명의 환자를 모집하였으나, 그 중 39명만이 분석되었다. 신장이식 후 3개월 시점에서 임상적, 이화학적 검사 결과로부터 치료 결과를 독성발현군, 치료적정군, 치료 부족군으로 분류하였다. 투약 전후의 TPMT 활성도를 paired t-test로 비교하여 TPMT 활성의 유도를 관찰하였다. TPMT 활성도와 6-TGN의 농도의 상관관계를 분석하였고 치료효과군에 따른 TPMT 활성도 또는 6-TGN 농도와의 관련성을 분석하기 위하여 로지스틱 회귀분석올 실행하였다. 결 과 : Azathioprine으로 면역억제요법을 시행하는 신장 이식환자를 대상으로 치료시작 전에 적혈구내의 TPMT 활성도를 측정한 결과, TPMT 활성도는 $11.9{\pm}3.1\;(mean{\pm}SD)$ (nmole/hr/mL packed RBC)로 나타났으며, 이러한 결과는 기존 정상 한국인의 분포$(12.0{\pm}2.9)$와 유사하였다. Azathioprine 면역억제요법 시행 후 TPMT 활성도는 $15.5{\pm}4.0\;(mean{\pm}SD)$ (nmole/hr/mL packed RBC)으로 증가하였고 이러한 TPMT 활성도의 증가는 통계적으로 유의하였다(p<0.01). Azathioprine의 활성 대사물인 6-TGN의 적혈구내의 농도와 azathioprine 투여 전 또는 투여 후의 TPMT 활성도와의 역상관성 을 관찰할 수 없었다(p>0.05). 치료 전 TPMT 활성도 또는 6-TGN 농도와 환자 개개인의 치료 결과와는 관련성이 없었다(p>0.05). 결 론 : 이상의 결과로부터 환자 개개인의 TPMT 활성도 검색은 심각한 부작용 및 치료 부족에 의한 거부반응을 예측할 수 있는 지표로 이용되기 어렵다. 이러한 결과는 한국인의 TPMT 활성도의 분포가 unimodal하여 개개인의 활성도 차이가 심하지 않기 때문인 것으로 사료되며, 이후에 관련된 연구가 필요하다.

Background/Aims: Hepatitis B virus (HBV) is associated with clinically significant chronic infection that may lead to the development of cirrhosis or even hepatocellular carcinoma. However, interferon alpha is effective in only 25-40% of chronic hepatitis B patients. The purpose of this study was to evaluate the effectiveness of interferon and lamivudine combination treatment comparing with interferon alone. Methods : Twenty patients with chronic hepatitis B(moderate to severe activity) were randomized to with interferon alone (11 patients) or combination (9 patients) therapy for 24 weeks. The patients were monthly evaluated, biochemically and serologically. Results : There was no statistical difference between both groups in HBeAg seroconversion rate and ALT normalizaion rate at the end of treatment. But, HBV DNA suppression rate was significantly higher in combination group (100%) than the interferon alone group (54%). No serious side effects were noted in both groups. Conclusion : Combinaton therapy with alpha interferon plus lamivudine given for 24 weeks appears safe and is well tolerated. But, combination therapy was no more efficient than interferon alone in HBeAg seroconversion except HBV DNA suppression rate during the treatment period.

연구배경 메타분석은 독립적으로 수행된 여러 개의 임상시험 결과들을 결합하여 분석하므로써 연구대상수의 제한을 극복하고 통계적 검정력을 높여 약물의 진정한 효능평가를 가능하게 한다. 본 연구에서는 이러한 장점을 갖는 메타분석방법을 적용하여 항고혈압제 사용이 심혈관 질환의 발생에 미치는 효능에 관하여 지금까지 일관되지 않은 연구 결과들을 정량적으로 요약하여 제시하고자하였다. 방 법 1980년대부터 1998년 사이에 출판된 연구 중 무작위배정 비교 임상시험(randomized controlled clinical trial)을 대상으로 삼았으며, 모든 종류의 항고혈압제에 대한 연구와 모든 형태의 투여 방법 (단독, 병용, 혹은 단계적 항고혈압제 사용)을 포함시켰다. 항고혈압제 투여군과 위약군(혹은 비처치군)간의 환자 배정이 무작위로 이루어진 연구, 최소한 2년 이상의 추적관찰기간올 가지는 연구로 제한하였으며 연구시작시점에 이미 관상동맥질환 혹은 뇌졸중을 가지고 있는 환자가 대상이 된 연구는 제외하였다. 총 11개의 논문에 대하여 상대위험도의 동질성 검정을 수행하고, 종합적 관련도 지표를 Mantel-Haenszel법을 사용하여 산출하였다. 결 과 관상동맥 심질환에 대한 누적상대위험도(Cumulative RR)는 0.82(0.727-0.97)로서 항고혈압제로 치료를 받은 군이 위약군에 비하여 전체 관상동맥심질환이 발생할 상대위험도는 0.82배로서 보호효과를 갖는 것으로 나타났으며 통계적으로도 유의하였다. 심근경색증에 대한 누적상대위험도는 0.77(0.623-0.916)로서 항고혈압제로 치료받은 군이 위약군에 비하여 MI의 발생에 대하여 0.77로서 보호효과를 갖는 것으로 나타났으며 역시 통계적으로도 유의하였다. 결 론 항고혈압제의 심혈관 질환 예방효과에 관한 무작위 배정 임상시험에 대한 메타분석을 시행한 결과 항고혈압제는 전체 심혈관질환 및 심근경색증의 발생에 대한 보호효과를 가지는 것으로 나타났으며 통계적으로도 유의한 값을 얻을 수 있었다.

Background: We present a case whose plasma cyclosporine concentrations were markedly decreased after adding antituberculosis medications. To assess the effect of rifampin on this pharmacokinetic interaction, we evaluated the pharmacokinetic changes of cyclosporine in kidney-transplanted patients with tuberculosis before and after withdrawing rifampin. Methods : Two separate full pharmacokinetic studies of cyclosporine were performed in four kidney recipients with tuberculosis before and one month after withdrawing rifampin from antituberculosis medications. Multiple blood samples were repeatedly drawn after morning oral dose of cyclosporine, and cyclosporine concentrations were determined by HPLC method. Pharmacokinetic parameters were estimated from noncompartmental method using $WinNonlin{\circledR}$ Results : After withdrawing rifampin, changing patterns of all pharmacokinetic parameters were consistent in all 4 subjects. Corrected Cmax and AUC estimated on the same 100mg dose basis were significantly increased from $291.1{\pm}54.1$ ng/ml to $950.7{\pm}174.7$ ng/ml and from $1483.1{\pm}92.0$ ng/ml ${\cdot}$ h to $6047.2{\pm}666.6$ ng /ml ${\cdot}$ hr, respectively (p($19.8{\pm}3.5$ L/kg) was decreased to $6.0{\pm}0.9$ L/kg after withdrawing rifampin. However, the prolongation of halflife was not statistically significant $(6.1{\pm}1.7 hour vs)$ $10.6{\pm}1.1)$. Conclusions : These results strongly suggest that rifampin markedly decrease the plasma concentration of cyclosporine coadministered through pharmacokinetic interaction, and careful dose readjustment should be considered from frequent monitoring of plasma cyclosporine concentrations in patients taking both cyclosporine and antituberculosis medications including rifampin.

Background: Transdermal absorption pharmacokinetics of diclofenac diethylammonium(DEA) plaster $(Rheumastop{\circledR})$ were estimated after single and multiple application in normal healthy subjects. Methods : Single plaster of 120 mg diclofenac DEA was applied to upper arm of 14 healthy male subjects for 24 hours and replaced with new plaster every 24 hours for following 14 days. Serial blood samples were drawn after the first dose and the last dose of the plaster and intermittent blood samples were drawn at 3, 5, 7 and 10 days of the study. Diclofenac concentrations in plasma, urine and plaster were determined by high performance liquid chromatography method. Pharmacokinetic parameters were estimated by both noncompartmental analysis and compartmental analysis of 2-compartment, 2-segment simultaneous input model with using $(NONMEM{\circledR})$ Results : The amount of diclofenac absorbed during 24 hour application of each diclofenac DEA plaster was estimated to $6.6{\pm}3.5$ mg and was corresponded to 6.9 % of total amount of diclofenac measured in the in tact plaster(average 95.17 mg). After the first dose of a diclofenac plaster, the average peak plasma concentration was reached to maximum concentration $(7.4{\pm}3.6 ng/ml)$ at $12.4{\pm}9.2$ hour. After multiple doses of diclofenac DEA plaster, the plasma concentration reached to peak level $(15.9{\pm}11.7 ng/ml)$ at $7.9{\pm}7.4$ hours, then concentrations were declined very slowly to $(10.0{\pm}5.1 ng/ml)$ at the time of next application. The mean AUC of diclofenac at steady state was estimated to $273{\pm}205 ng/ml$ h. From the compartmental model for the transdermal absorption of diclofenac DEA plaster, $75{\pm}14$ % of diclofenac dose was described by the burst zero order input model and the remained was by slow first order input model. The estimated volume of distribution (Vd/F) was estimated to $2.2{\pm}0.8$ L/kg and half life was $3.4{\pm}0.8$ hour. Conclusions : The diclofenac DEA plaster which shows initial burst and slow continuous input absorption kinetics appears to be able to maintain constant plasma level during 24 hour application. The measured plasma concentration-time profiles at steady-state are expected to be adequate for therapeutic effect, taking into account the comparable results to those from twice a day application of 185 mg diclofenac HEP plaster of which clinical effect has been well established. However, further clinical trials in patients are remained to document the clinical effects of this new diclofenac plaster.

The dose-response relationships of a drug are quite different among subjects due to pharmacokinetic and/or pharmacodynamic variations. The quantitative estimation of pharmacokinetic and/or pharmacodynamic characteristics of an individual subject is required for designing the optimum individualized dosage regimen for the subject. Concentration controlled pharmacotherapy can be one approach to minimize the inappropriate dosing caused by the pharmacokinetic variation. This article introduces some basic pharmacokinetic/pharmacodynamic concepts to understand the dose-response relationship of a given drug and to design optimum pharmacotherapy in a given patient with the data derived from therapeutic drug monitoring and/or literatures.

Many drugs are marketed by more than one pharmaceutical manufacturer. Because of the plethora of drug products containing the same amount of active drug, physicians, pharmacists, and others who prescribe, dispense, or purchase drugs must select generic products that produce an equivalent therapeutic effect to the brand product. Bioequivalent drug products are pharmaceutical equivalents that have similar bioavailability when given in the same molar dose. Therapeutic equivalents are drug products that contain the same therapeutically active drug that should give the same therapeutic effect and have equal potential for adverse effects under conditions set forth in the labels of these drug products. Therapeutic equivalent drug products must be (1) safe and effective, (2) pharmaceutical equivalents, (3) bioequivalent, (4) adequately labeled, and (5) manufactured in compliance with current good manufacturing practices. Generic subsitution is the process of dispensing a different brand or unbranded drug product in place of the prescribed drug product. The substituted drug product contains the same active ingredient or therapeutic moiety. This process requires the physician's permission.

Therapeutic drug monitoring (TDM) among various fields of clinical pharmacology plays the vital role in order to achieve the indivisualization of optimal drug therapy, which is the process of maximizing therapeutic effects and minimizing side effecs, simultaneously. Variable drug responses are largely due to the individual pharmacokinetic variations. Therefore in TDM it is very important to keep optimal drug concentrations, which makes it possible to optimize the clinical outcomes of each patient. In recent, the introduction of clinical pharmacokinetic principles and development of assay methods makes TDM more prevalent. This article describes the clinical significance, functions, and applications of TDM in several aspects. TDM indications, concepts and examples of therapeutic range are also described. The features which should be strived for in each step of TDM process (the decision to request a drug level, blood sampling, laboratory measurement, clinical interpretation of drug concentration, and production of individualized dosage regimen and dosage adjustment) are discussed.

Drugs administered to patients are biotransformed by a number of drug metabolizing enzymes. Considerable parts of drugs as well as environmental chemicals are metabolized by the hepatic cytochrome P450 system. Drug interactions of metabolism have varying clinical relevance. Some of the drugs can induce their own metabolism and also affect the metabolism of other drugs. Similarly, drugs metabolized by the same enzyme system can act as competitive inhibitors and decrease the metabolism of other drugs. Furthermore, some drugs can inhibit other drugs through non-competitive manner. There has been much improvement on the pharmacogenetics that deal with variability in drug response due to heredity. It is now known that there is a great deal of individual variability in the metabolic capacity of the hepatic enzyme systems and the degree to which it may be induced or inhibited by drugs. Although it is not easy to predict the extent of an interaction in an individual patient, optimum drug therapy may be accomplished by understanding the mechanism of enzyme induction or inhibition and the principle of pharmacogenetics as well.