• 제목/요약/키워드: Model-drug distribution

검색결과 79건 처리시간 0.025초

다층 배양된 암세포에서 파크리탁셀의 항증식효과 분석 (Anti-proliferative Effect of Paclitaxel in Multicellular Layers of Human Cancer Cells)

  • 강춘모;이주호;차정호;구효정
    • Journal of Pharmaceutical Investigation
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    • 제36권1호
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    • pp.1-9
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    • 2006
  • Human solid tumors exhibit a multicellular resistance (MCR) resulting from limited drug penetration and decreased sensitivity of tumor cells when interacting with their microenvironments. Multicellular cultures represent solid tumor condition in vivo and provide clinically relevant data. There is little data on antitumor effect of paclitaxel (PTX) in multicellular cultures although its MCR has been demonstrated. In the present study, we evaluated antiproliferative effects of PTX in multicellular layers (MCL) of DLD-1 human colorectal carcinoma cells. BrdU labeling index (LI), thickness of MCL, cell cycle distribution and cellular uptake of calcein were measured before and after exposure to PTX at 0.1 to 50 ${\mu}M$ for 24, 48 and 72 hrs. BrdU LI and thickness of MCL showed a concentration- and time-dependent decrease and the changes in both parameters were similar, i.e., 34.2% and 40.6% decrease in BrdU LI and thickness, respectively, when exposed to $50\;{\mu}M$ for 72 hr. The DLD-1 cells grown in MCL showed increase in $%G_{0}/G_{1}$ and resistance to cell cycle arrest and apoptosis compared to monolayers. Calcein uptake in MCL did not change upon PTX exposure, indicating technical problems in multicellular system. Overall, these data indicate that antitumor activity of PTX may be limited in human solid tumors (a multicellular system) and MCL may be an appropriate model to study further pharmacodynamics of PTX.

The Changes of P-glycoprotein Activity by Interferon-γ and Tumor Necrosis Factor-α in Primary and Immortalized Human Brain Microvascular Endothelial Cells

  • Lee, Na-Young;Rieckmann, Peter;Kang, Young-Sook
    • Biomolecules & Therapeutics
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    • 제20권3호
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    • pp.293-298
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    • 2012
  • The purpose of this study was to investigate the modification of expression and functionality of the drug transporter P-glycoprotein (P-gp) by tumor necrosis factor-alpha (TNF-${\alpha}$) and interferon-gamma (IFN-${\gamma}$) at the blood-brain barrier (BBB). We used immortalized human brain microvessel endothelial cells (iHBMEC) and primary human brain microvessel endothelial cells (pHBMEC) as in vitro BBB model. To investigate the change of p-gp expression, we carried out real time PCR analysis and Western blotting. To test the change of p-gp activity, we performed rhodamin123 (Rh123) accumulation study in the cells. In results of real time PCR analysis, the P-gp mRNA expression was increased by TNF-${\alpha}$ or IFN-${\gamma}$ treatment for 24 hr in both cell types. However, 48 hr treatment of TNF-${\alpha}$ or IFN-${\gamma}$ did not affect P-gp mRNA expression. In addition, co-treatment of TNF-${\alpha}$ and IFN-${\gamma}$ markedly increased the P-gp mRNA expression in both cells. TNF-${\alpha}$ or IFN-${\gamma}$ did not influence P-gp protein expression whatever the concentration of cytokines or duration of treatment in both cells. However, P-gp expression was increased after treatments of both cytokines together in iHBMEC cells only compared with untreated control. Furthermore, in both cell lines, TNF-${\alpha}$ or IFN-${\gamma}$ induced significant decrease of P-gp activity for 24 hr treatment. And, both cytokines combination treatment also decreased significantly P-gp activity. These results suggest that P-gp expression and function at the BBB is modulated by TNF-${\alpha}$ or/and IFN-${\gamma}$. Therefore, the distribution of P-gp depending drugs in the central nervous system can be modulated by neurological inflammatory diseases.

병원중심 가정간호 사업의 평가 연구 -외래 관절염 환자를 대상으로 - (Effects of Hospital-based Home Care Demonstration Project on Physical and Emotional Problems and Cost - effectiveness of Patients having Arthritis)

  • 임난영;김성윤;이은옥;이인숙
    • 근관절건강학회지
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    • 제3권1호
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    • pp.4-22
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    • 1996
  • Purposes of this study were to identify a hospital-based home care model and to improve the physical, emotional and economical effectiveness of arthritic patients through medical and nursing team approach. The design in nonequivalent control group pretest-posttest design with matched samples in terms of age, sex and disease severity. Fifty two patients in each group were assigned in Seoul, Kyunggi, Kangwon and Kwangju. Before and after 6-month period of home care, level of pain, duration of morning stiffness, Richie Index, ADL, self efficacy, depression, cost expenditure were measured. Nine patients were excluded from the control group in the period of study because of denial of participation. Contents of home care provided to the experimental group include mainly distribution of prescribed drugs, 'assessment of patients' condition and side-reactions of drug. All of the information related to the home care patient were reported to the physician. On the bases of these data, the physician prescribe the specific drugs to each patient. Each patient visited the physician every 2 or 3 month for laboratory test. Patients assigned to the control group visited the outpatient clinic once a month as usual. Null hypotheses were selected because physicians concerned about the ineffective change of patients' conditions due to indirect communication with patients through nurses. Level of pain, Richie index, ADL, self-efficacy, depression, duration of morning stiffness and direct medical cost were the home care provided to them. If a family member accompany in a home care group can save 10,676 Won/month in Seoul, 34,000 Won/month in other districts. Other in-direct cost for transportation and meal can also be saved. In conclusion, those patients with low level of ADL, high level of pain and Richie index, living in the remote area definitely need the home care.

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국가별 행정체계 특성을 반영한 인공지능 활용 해외 주소데이터 품질검증 기법 (Overseas Address Data Quality Verification Technique using Artificial Intelligence Reflecting the Characteristics of Administrative System)

  • 김진실;이경희;조완섭
    • 한국빅데이터학회지
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    • 제7권2호
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    • pp.1-9
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    • 2022
  • 글로벌 시대에 들어서면서 수입식품 안전관리에 대한 중요성이 증가하고 있다. 해외 식품업체 주소정보는 수입식품 안전관리를 위한 핵심 정보로써 식품위해 발생시 신속한 대처와 사후관리를 위해 반드시 검증되어야 한다. 그러나 각국의 주소체계가 다른 관계로 하나의 검증시스템이 모든 국가의 주소를 검증할 수는 없다. 또한, 주소검증은 사용하는 분야에 따라 검정목적이 상이할 수 있다. 본 논문에서는 주어진 해외 식품업체 주소로부터 해당 국가의 행정구역 레벨로 분류하는 문제를 다룬다. 수입식품 안전관리를 정확하고 효율적으로 하기 위하여 수입식품제조업체 주소를 해당 국가의 행정구역 수준으로 정확하게 매칭하는 것이 필요하다. 수입식품이 생산·제조되는 위치와 식품제조에 영향을 줄 수 있는 환경정보, 재난재해 정보를 결합함으로써 선제적 수입식품 안전관리가 가능하다. 그러나, 일부 국가에서는 주소를 표기할 때 행정구역 레벨명을 생략하여 작성하고 있으며, 동일한 지명이 여러 행정구역 레벨에서 중복되는 경우가 있어 주소로부터 행정구역 레벨을 정확히 분류하는 일은 쉽지 않다. 본 연구에서는 이러한 경우에 적합한 딥러닝 기반 행정구역 레벨 분류 모델을 제안하고, 실제 해외 식품회사 주소 데이터에 대하여 검증한다. 구체적으로 다중 레이블 분류 모델에서 멱집합(Label Powerset)을 이용해 훈련하는 방식을 사용한다. 제안된 기법의 검증을 위해 식약처에 등록된 에콰도르 및 베트남에 있는 해외 제조업소 주소에 대하여 정확도를 검증하였으며, 기존의 분류 모델보다 정확도가 각각 28.1% 및 13% 정도 향상되었다.

다제 내성 폐결핵환자의 폐절제술에 관한 연구 (Pulmonary Resection in the Treatment of Multidrug-Resistant Tuberculosis)

  • 권은수;하현철;황수희;이흥렬;박승규;송선대
    • Tuberculosis and Respiratory Diseases
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    • 제45권6호
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    • pp.1143-1153
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    • 1998
  • 연구배경 : 다제내성 폐결핵 환자에서 폐절제술이 다제내성 폐결핵의 치료에 미치는 영향에 관심을 두어 폐절제술과 화학요법 즉 병합요법의 치료 효과를 화학치료 효과와 비교 분석하여 그 결과를 지표로 다제내성 폐결핵의 치료효과를 증가시키는 데 지표를 삼고자 본 연구를 시행하였다. 방 법 : 국립마산결핵병원에서 1993년 1월부터 1997년 12월까지 폐결핵 환자 중 폐절제술을 시행 받은 79예 중 INH와 RFP을 포함하는 2제 이상의 항결핵제에 내성을 가지는 다제내성폐결핵 41예를 대상으로 진료기록을 중심으로 후향적으로 조사하였다. 전체 41예의 환자는 흉부 X선 소견상 한쪽 폐야에 국한된 병변을 절제한 국소병변군과 주병변의 절제후 잔류병 변에 공동이 남은 잔류공동군과 침윤성 소견이 남은 잔류침윤군으로 나누어 각 군의 술후 균음전율, 전체치료반응율을 측정하여 Goble 등에 의한 다제내성폐결핵에 대한 화화치료의 균음전율, 전체치료반응율과 비교하였다. 균음전율의 비교는 단일분율의 분석 (analysis of single proportion)중에 이항분포(Binomial distribution)를 이용한 직접산출법(exact model)을 이용하였고, 전체치료반응율은 단일비율의 분석(analysis of single rate)중에 포아송 분포(poisson distribution)를 이용한 직접산출법(exact model)을 이용하여 p 값을 구하였고, 통계화적 의의는 p 값이 0.05 이하일 때 그 유의성을 인정하였다. 결 과 : 전체 대상 환자는 41예로 남자가 31예, 여자가 10예이었고 16세에서 60세의 연령 분포를 보였으며 중앙치가 31 세였다. 평균 2.3회의 화학치료 과거력을 가지고 있으며 술전에 평균 4.9제의 약제를 사용하였고 술전 평균 내성 약제수는 4.8제이었다. 수술은 전폐절제술이 14예, 폐엽절제술이 24예, 구역절제술이 1예, 폐업절제술과 구역절제술을 병합한 경우가 2예이었다. 단순 흉부 X-선 사진상 국소병변군이 26예, 잔류공동군이 7예, 잔류침윤군이 8예였다. 전체환자군에서 균음전율은 90.9%로 통계적으로 유의하게 높았으며 치료실패 5예와 치료종결후 추적관찰이 가능했던 21예 중 재발 2예가 나타나 전체치료반응율은 73.1%로 통계적으로 유의하게 높았다. 국소병변군의 술후 균음전율은 100%로 통계적 유의성이 있었고, 전체 치료반응율은 93.3%로 통계적으로 유의한 차이를 나타내었으며 술후 투약기간은 평균 12.2개월이었다. 국소병변군증 술후에 일차약으로 투약한 군의 전체치료반응율은 75%로 통계적으로 유의하게 좋은 결과를 보였고 술후 투약기간은 평균 7.5개월이었다. 잔류공동군의 수술에 악한 균음전율은 75%로 통계적으로 차이가 없었으며, 전체치료반응율은 14.19%로 통계적으로 유의하게 낮은 결과를 보였고 술후 투약기간은 평균 16.7개월이었다. 잔류침윤군의 술후 균음전율은 83.3%로 통계적으로 차이가 없었고, 전체치료반응율은 100%로 통계적으로 유의하게 높았고 술후 투약기간은 평균 11.8개월이었다. 결 론 : 다제내성 폐결핵의 화학치료 과정 중 적절한 시기에 수술을 시행하는 것은 그 치료결과를 상승시키는 효과가 있다. 그러나, 술후에 공동이 남을 환자들은 가능한 광범위 절제를 시행하여야 하며 모든 공동의 절제가 불가능한 경우는 수술하지 않는 것이 타당할 것으로 판단된다. 국소병변군과 잔류병변군증의 잔류침윤군의 술후 투약기간은 평균 12개월 정도로 굳이 18개월 이상의 투약이 아니라 하더라도 그 결과는 양호하며 국소병변군에서 술후 일차약제의 사용도 치료효과를 상승시키는 데 장애가 되지 않는다고 조심스럽게 말할 수 있겠다.

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금속도재관으로 수복된 Abfraction lesion이 있는 치아에 가해지는 교합력의 응력 분포 분석 (Analysis of stress distribution of tooth restored with metal-ceramic crown covering abfraction lesion according to its finish line location under occlusal load)

  • 김지환;윤철욱;김태현;김한성;우대곤;이근우;심준성
    • 대한치과보철학회지
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    • 제52권4호
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    • pp.305-311
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    • 2014
  • 목적: 다양한 원인으로 발생된 Abfraction 병소가 있는 치아를 금속도재관으로 수복 할 경우, 변연의 위치에 따라 예후가 다양해질 수 있다. 수복물의 장기적 성공을 검증하기 위해서는 응력분포의 분석이 필요하지만 금속도재관이 abfraction 병소의 적응증인 경우 금속도재관이 응력 분포에 미치는 영향을 밝히는 연구는 아직 없다. 본 연구의 목적은 abfraction 병소가 있는 치아를 수복하는 금속도재관이 바람직한 응력 분포를 나타낼 수 있는 조건을 알아 보고자 함이다. 재료 및 방법: 치아, 주위 조직과 금속 도재관의 외형을 반영한 2차원 유한 요소모델을 제작하고 144 N의 편심 교합력 하에서의 응력분포를 유한요소 분석법으로 분석하였다. 금속 도재관의 변연 위치를 쐐기모양의 결손부의 하연에(Group 0), 그리고 결손부의 하연보다 1 mm 하방(Group 1)과 2mm 하방(Group2)에 위치시켰다. 결과: Group 0에서 von Mises stress는 금속 도재관의 변연과 결손부의 첨부에 집중 되었고 협측 변연의 응력은 설측 부위로 분포되었다. Group 1과 Group 2에서의 응력분포양상은 비슷하게 나타났다. 응력은 결손부의 첨부에 집중되지만 협측과 설측의 응력띠는 서로 분리된 양상으로 나타났다. 결론: 금속도재관의 변연을 Abfraction 병소의 하연에 설정할 경우, 금속도재관은 Abfraction 병소의 첨부에 응력을 집중시킨다.

록시스로마이신의 정맥주사 후 육계에서의 약물동태학적 분석 (Pharmacomkinetics of Roxithromycin after Intravenous Administration in Broilers)

  • 임종환;박병권;김명석;황윤환;윤효인
    • 한국임상수의학회지
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    • 제23권2호
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    • pp.87-90
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    • 2006
  • 본 연구는 록시스로마이신의 정맥주사 후 육계에서의 약물동태학적 특성을 조사한것으로, 이때 록시스로마이신은 체중당 20 mg/kg 용량으로 정맥주사하였다. 시간에 따라 채혈하여 혈장을 분리한 후 액체크로마토그래프/질량분석기를 이용하여 혈장내 록시스로마이신의 농도를 측정하였다. 혈장내 록시스로마신 농도-시간 그래프의 분석은 two-compartment open model을 적용하는 것이 가장 적합하였다. 육계에서의 록시스로마이신의 약물동태학적 부변수의 값은 다음과 같았다. 소실 반감기 =$5.83{\pm}1.79h$, 평균체류 =$6.33{\pm}0.32h$, 청소율 =$0.55{\pm}0.15L/h/kg$ 및 정상상태 분포용적 = $3.47{\pm}0.84L/kg$ 육계에서 정맥주사 후 록시스로마이신은 늦은 소실과 체내 고른 분포의 약물동태학적 특성을 나타내었다. 록시스로마이신의 육계에 적용할 때에는 약물제형, 최적 용량용법, 임상효과 및 반복투여에 대한 내성등의 연구가 추후 요구된다.

Pharmacokinetics of amikacin in plasma of healthy goats after intravenous injection once daily for three days

  • Naseem, Sania;Sultana, Mudasir;Raina, Rajinder;Pankaj, Nrip Kishore;Verma, Pawan Kumar;Nasir, Nasir Ahmad;Ahanger, Azad Ahmad;Rahman, Shafiqur;Prawez, Shahid
    • 대한수의학회지
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    • 제51권4호
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    • pp.253-257
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    • 2011
  • Amikacin is a semisynthetic derivative of kanamycin and primarily active against aerobic Gram-negative-pathogens with limited activity against Gram-positive bacteria. Meager study was reported on pharmacokinetic data on multi-days administration of amikacin. Hence, pharmacokinetics study was done in five clinically healthy goats (n = 5), after intravenous bolus injection of amikacin sulfate at the dose rate of 10 mg/kg body weight daily for three consecutive days. The amikacin concentrations in plasma and pharmacokinetics-parameters were analyzed by using microbiological assay technique and noncompartmental open-model, respectively. The mean peak plasma concentrations (Mean ${\pm}$ SD) of amikacin at time zero ($Cp^{0}$) was $114.19{\pm}20.78$ and $128.67{\pm}14.37{\mu}g/mL$, on day 1st and 3rd, respectively. The mean elimination half-life ($t_{1/2}ke$) was $1.00{\pm}0.28h$ on day 1st and $1.22{\pm}0.29h$ on day 3rd. Mean of area under concentration-time curve ($AUC_{0{\rightarrow}{\infty}}$) was $158.26{\pm}60.10$ and $159.70{\pm}22.74{\mu}g.h/mL$, on day 1st and 3rd respectively. The total body clearance ($Cl_{B}$) and volume of distribution at steady state (Vdss) on day 1st and 3rd were $Cl_{B}=0.07{\pm}0.02$ and $0.06{\pm}0.01L/h.kg$ and $Vdss=0.10{\pm}0.03$ and $0.11{\pm}0.05L/kg$, respectively. No-significant difference was noted in both drug-plasma concentration and pharmacokinetics-parameters, respectively. Amikacin concentration in plasma was found higher up-to 4 h and 6 h onward on down-ward trends favour to reduce toxicity. Which also support the pharmacokinetic-pharmacodynamic way of dosing of aminoglycosides and hence, amikacin may be administered 10 mg/kg intravenously daily to treat principally Gram-negative pathogens and limitedly Gram-positive-pathogens.

"뇌공포자론(雷公炮炙論)"에 관한 연구 - 포제(炮制)를 중심으로 - (A Study On "LeiGongPaoZhiLun(雷公炮炙論)" - Centering Of Processing Of Medicinal -)

  • 하홍기;김기욱;박현국
    • 대한한의학원전학회지
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    • 제24권2호
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    • pp.23-50
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    • 2011
  • "LeiGongPaoZhiLun" is the first pharmaceutical book, and there are various opinion on when LeiXiao(雷斅), the author lived. From the aspect of several data, it is appropriate most that LeiXiao live in the period of Sui(隋) Dynasty, like SuSong(蘇頌) in the Sung Dynasty said, This book was not made at one time by one person. At the beginning, it was written by LeiXiao and the later generations enlarged to finish. The original of "LeiGongPaoZhiLun" disappeared already but a large amount of this book was quoted to "ZhengLeiBenCao(證類本草)" to be preserved. The contents of "LeiGongPaoZhiLun" are the first professional book about processing of medicinal, in which most of processing of medicinal that is generally used today, is included and some methods are unused. Besides, the regulations of this book are specific, the range is broad, and theoretical frame is established for the first time. This book has abundant contents, in which several processing of medicinal are written. There are 10 methods such as steaming(蒸法), boiling(煮法), baking(炮法), stir-frying(炒法), calcining(煅法), long time boiling(煉法), scorching(燒法), baking after wrapping(煨法), immersing(浸法), washing(洗法), flying(飛法), etc. How to remove some section that is not used for drug, how to separate according to medical use and region to be applied, how to smash, how to cut, how to dry, container for medicine, warning for making a prescription, time to make medicine and amount of medicine, how to distinguish superior and inferior and origin, how to make medicine partially, etc, are contained in this book. The contents of "LeiGongPaoZhiLun" can be mixture of processing of medicinal of medical scientists and taoists. In conclusion, however, the effect by the later medical generations of "LeiGongPaoZhiLun" was not great on processing of medicinal. It stemmed from the difference of processing of medicinal in this very taoistic book that realistic difficulties were disregarded by taoists for training and practical purpose, treatment that is the reason that later medical generations used processing of medicinal. Consequently, there is no great relation between the development of processing of medicinal in the Sung Dynasty and this book. "LeiGongYaoXingFu(雷公藥性賦)" that was abundant in medical market in Ming(明) and Qing(清) period has no relation with "LeiGongPaoZhiLun" is kind of a distribution-purposed book that was mnge in or after Ming Dynasty. However, since a book that is said to be written by 'LiGao(李杲)'PaoZhihis nof a dijust borrowed and focus on a brief summery, it is not desirable for beginners to learn medical knowledge. "LeiGongPaoZhiLun" is the first pharmaceutical book and is a model to show how a science in the history of the herb medicine generated and developed and how such a book is changed and modified to make a change of value.

수술후 급성 동통에 대한 Tramadol/Acetaminophen과 Codeine/Acetaminophen/Ibuprofen의 효과 발현시점과 진통효과의 비교 (COMPARISON OF TRAMADOL/ACETAMINOPHEN AND CODEINE/ACETAMINOPHEN/IBUPROFEN IN ONSET OF ANALGESIA AND ANALGESIC EFFICACY FOR POSTOPERATIVE ACUTE PAIN)

  • 정영수;김동기;김문기;김형준;차인호;한무영;이의웅
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제30권2호
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    • pp.143-149
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    • 2004
  • Background: Some clinical trials have reported that a new analgesic combination of tramadol and acetaminophen provides good efficacy in various pain models. For the more clinical uses of this agent, comparisons about the onset of analgesia and analgesic efficacy in the acute state of pain with the other drugs known as strong analgesics were needed. Purpose: The goal of this study was to compare the times to onset of analgesia and the other analgesic efficacy of 75 mg tramadol/650 mg acetaminophen and 20 mg codeine/500 mg acetaminophen/400 mg ibuprofen in the treatment of acute pain after oral surgery. Patients and Methods: Using a randomized, single-dose, parallel-group, single-center, and active-controlled test design, this clinical study compared the times to onset of analgesia using a two-stopwatch technique and the other analgesic efficacy of the single-dose tramadol/acetaminophen and codeine/acetaminophen/ibuprofen. These were assessed in 128 healthy subjects with pain from oral surgical procedures involving extraction of one or more impacted third molars requiring bone removal. From the time of pain development, the times to onset of perceptible and meaningful pain relief, pain intensity, pain relief, an overall assessment, and adverse events of the study medications were recorded for 6 hours. Results: The demographic distribution and baseline pain data in the two groups were statistically similar. The median times to onset of perceptible pain relief were 21.0 and 24.4 minutes in the tramadol/acetaminophen and codeine/acetaminophen/ibuprofen groups respectively and those to onset of meaningful pain relief were 56.4 and 57.3 minutes, which were statistically similar. The other efficacy variables such as mean total pain relief (TOTPAR) and the sum of pain intensity differences (SPID) were also similar in the early period after pain development and drug dosing. The safety of tramadol/acetaminophen was well tolerated and very comparable to that of codeine/acetaminophen/ibuprofen. Conclusions: In this acute dental pain model, the onset of analgesia and analgesic efficacy of tramadol/acetaminophen was comparable to that of codeine/acetaminophen/ibuprofen. These results showed that tramadol/acetaminophen was recommendable for fast and effective treatment in the management of postoperative acute pain.