安徽医科大学：《临床药理学 Clinical Pharmacology》课程教学资源（授课教案，英文版）New drugs development.pdf_大学文库

安徽医科大学国际教育学院教案与讲稿 or cell--free systems(非细胞系统) Intact cell lines:For example,some new drugs for tumors,the effects of the new drugs on tumor cell growth,cell cycle distribution,cell differentiation,or the induction of apoptosis can also be readily measured at this stage of drug development. Cell-free systems assays include to measure enzyme inhibition, receptor binding, protein-small molecule interactions, interference with components of important signal transduction pathways. [Drug Supply and Formulation] 3min (1)Prior to entering clinical trials,adequate drug supplies of pharmaceutical-grade material must be available. (2)bulk chemical synthesis protocols, natural product isolation, adequate amounts of raw materials for drug or its synthetic precursors [Preclinical Pharmacodynamic in Animal Models] 10min (1)The adequacy of any specific animal model depends on its validity,selectivity,predictability, and reproducibility. (2)Mouse and rat model systems have several advantages over the use of higher mammals for investigating mammalian biology and disease states. (3)In cancer chemotherapy,animal models are selected to simultaneously demonstrate antitumor efficacy and evaluate systemic toxicities in an intact organism. (4)Ideally,the tumor system in the animal model should be genetically stable over time. [Preclinical Pharmacokinetic Testing] 5min A well-designed drug development program should fully integrate pharmacokinetic and pharmacodynamic studies early in the preclinical testing process. Preclinical Toxicology] 5min Preclinical toxicological studies are required.Preclinical toxicological studies include acute and chronic toxicology [The definition of GCP and the significance of implementing GCP] 5min The definition of GCP GCP is the whole standard process of clinical trials,including design, organization,implementation,check,records,summarize and report. (1)To guarantee fully the rights,interests and healthy of the subjects. (2)To ensure accurate reliable scientific and real test data,for the clinical evaluation of drugs. (3)It is an effective measures to improve the level of management and supervision for new drug research in China. (4)It is an effective measures to narrow the gap of the level of drug clinical trials between the developed countries and China,to enter China's innovation good drugs into the international market. (5)It is benefit to implement clinical trials of international multi centers in the same period in China. (6)Enhance the constructions for clinical research organization. [Phase I clinical trial--Tolerance test] 10min Phase I clinical trial for drug include tolerance test and pharmacokinetic studies. 3

安徽医科大学国际教育学院教案与讲稿 3 or cell-free systems(非细胞系统）. Intact cell lines: For example, some new drugs for tumors, the effects of the new drugs on tumor cell growth, cell cycle distribution, cell differentiation, or the induction of apoptosis can also be readily measured at this stage of drug development. Cell-free systems assays include to measure ： enzyme inhibition, receptor binding, protein-small molecule interactions, interference with components of important signal transduction pathways. [Drug Supply and Formulation] 3min (1) Prior to entering clinical trials, adequate drug supplies of pharmaceutical-grade material must be available. (2) bulk chemical synthesis protocols, natural product isolation, adequate amounts of raw materials for drug or its synthetic precursors. [Preclinical Pharmacodynamic in Animal Models] 10min (1) The adequacy of any specific animal model depends on its validity, selectivity, predictability, and reproducibility. (2) Mouse and rat model systems have several advantages over the use of higher mammals for investigating mammalian biology and disease states. (3) In cancer chemotherapy, animal models are selected to simultaneously demonstrate antitumor efficacy and evaluate systemic toxicities in an intact organism. (4) Ideally, the tumor system in the animal model should be genetically stable over time. [Preclinical Pharmacokinetic Testing] 5min A well-designed drug development program should fully integrate pharmacokinetic and pharmacodynamic studies early in the preclinical testing process. [Preclinical Toxicology] 5min Preclinical toxicological studies are required. Preclinical toxicological studies include acute and chronic toxicology. [The definition of GCP and the significance of implementing GCP] 5min The definition of GCP :GCP is the whole standard process of clinical trials, including design, organization, implementation, check, records, summarize and report. (1) To guarantee fully the rights, interests and healthy of the subjects. (2) To ensure accurate, reliable, scientific and real test data, for the clinical evaluation of drugs. (3) It is an effective measures to improve the level of management and supervision for new drug research in China. (4) It is an effective measures to narrow the gap of the level of drug clinical trials between the developed countries and China, to enter China's innovation good drugs into the international market. (5) It is benefit to implement clinical trials of international multi centers in the same period in China. (6) Enhance the constructions for clinical research organization. [PhaseⅠ clinical trial--Tolerance test] 10min Phase clinical trial for dru Ⅰ g include tolerance test and pharmacokinetic studies

安徽医科大学国际教育学院教案与讲稿 The purpose: To study the drug dose for tolerance, To understand the rules of absorption,distribution,metabolism,elimination of the drug, To provide the safe and effective protocol for phase II. (1)How to group the subjects: Small toxicity,rich experience,a fewer groups might be given: Strong effect or the bigger toxicity drugs,dosage spaces should be narrow. (2)How to determine the minimum first dose: DThe first drug dose can be used by 1/10 of the same dose of clinical therapy generally 2Using 1/600 of the LD50 of sensitive animals or 1/60 of the minimum efficient dose, 3First try dose for human may be used by 1/5-1/3 of largest tolerability dose according to the surface area of big animals(dog). 4 Starting doses for clinical studies were calculated as one-third the lowest toxic dose for the most sensitive animal species,either monkey or dog. 5 In 1979,FDA guidelines recommended that one-tenth the dose that causes Lethality in 10%of the treated mice (LD10)could be selected as the starting dose for clinical trials. (3)The determination of maximum dosage: The maximum dose can be used as same as the volume of similar drugs for clinical single treatment. [Pharmacokinetic study] 5min Pharmacokinetic study can be carried out combining with tolerance test. Tolerance test and pharmacokinetic studies should be implemented with an single dose and multi doses. [The purposes of Phase II clinical triall 2min To evaluate the effect and safety. To provide the basis of research design and administration dosage for phase IlI clinical trials. Preparation for phasesⅡclinical trials】 3min (1)To choose responsible clinical trials unit and main researchers (2)To provide the SFDA approval of clinical trials, (3)To draft clinical trial protocol and case register format(CRF); (4)To prepare new drug,controlled drugs,random table,etc.; (5)The trial protocol is approved by the ethics committee; (6)To select subjects,and sign informed consent form. [Design principles for clinical trial] 5min The design of phase II clinical trial should conforms to the principles,namely:four "R" principles: Representative, Repeatability, Random, Rationality. The contrast test,control groups. 5min Including parallel-group and cross controlled trial 4

安徽医科大学国际教育学院教案与讲稿 4 The purpose: To study the drug dose for tolerance, To understand the rules of absorption, distribution, metabolism, elimination of the drug, To provide the safe and effective protocol for phase . Ⅱ (1) How to group the subjects: Small toxicity, rich experience, a fewer groups might be given; Strong effect or the bigger toxicity drugs, dosage spaces should be narrow. (2)How to determine the minimum first dose: ①The first drug dose can be used by 1/10 of the same dose of clinical therapy generally. ②Using 1/600 of the LD50 of sensitive animals or 1/60 of the minimum efficient dose, ③First try dose for human may be used by 1/5-1/3 of largest tolerability dose according to the surface area of big animals (dog). ④ Starting doses for clinical studies were calculated as one-third the lowest toxic dose for the most sensitive animal species, either monkey or dog. ⑤ In 1979, FDA guidelines recommended that one-tenth the dose that causes Lethality in 10% of the treated mice (LD10) could be selected as the starting dose for clinical trials. (3) The determination of maximum dosage: The maximum dose can be used as same as the volume of similar drugs for clinical single treatment. [Pharmacokinetic study] 5min Pharmacokinetic study can be carried out combining with tolerance test. Tolerance test and pharmacokinetic studies should be implemented with an single dose and multi doses. [The purposes of Phase II clinical trial] 2min To evaluate the effect and safety. To provide the basis of research design and administration dosage for phase III clinical trials. [Preparation for phasesⅡ clinical trials ] 3min (1) To choose responsible clinical trials unit and main researchers (2) To provide the SFDA approval of clinical trials; (3) To draft clinical trial protocol and case register format (CRF); (4) To prepare new drug, controlled drugs, random table, etc.; (5) The trial protocol is approved by the ethics committee; (6) To select subjects, and sign informed consent form. [Design principles for clinical trial] 5min The design of phase Ⅱ clinical trial should conforms to the principles, namely: four “R” principles: Representative, Repeatability, Random, Rationality. [The contrast test, control groups.] 5min Including parallel-group and cross controlled trial

安徽医科大学国际教育学院教案与讲稿 person,whose liver or kidney is disfunctional, or cardiopulmonary function is not complete. Children,pregnant or lactation women and the person with drug allergy. [Assessment of responsel 2min There are 4 grades:cure or clinical relief,excellence,improvement,failure. Efficient(%):the number of(cure +excellence)/the number of total cases*100% Some individual cases,which can't be evaluated,should be listed. [Adverse reaction evaluation 3min Adverse reactions includes clinical and laboratory abnormal reaction. Three type,namely A,B and C. Type A reaction:strong pharmacological function drug or the interaction with other drugs. Type A response could be observed or examined in clinical trials. Type B reaction,can be life-threatening and can't be predicted. Once happen,should be reported immediately to the organizer and drug management department. Type C reaction often appears with disease,and is not found or perceived in drugs trials,and is found through the epidemiological study. Phase III clinical triall 2min Phase IlI clinical trial is the stage for confirmation effect. Its purpose: to test the effect and safety of drug further, to provide adequate basis for drug registration eventually.Generally,phase III clinical trial should be random,blinded and controlled trial with sufficient sample size. [Phase IV clinical trial] 3min Phase IV clinical trial is the clinical trials of postmarketing,namely postmarketing surveillance Its purpose is: (1)To investigate the curative effect and adverse reaction under the condition of widespread administration; (2)To evaluate the relationship between benefits and risks; (3)To improve administration dosage; (4)To know of the response,indications and adverse reaction further, (5)To guide clinical rational drug administration. [Drug bioequivalence test-The purpose and significance of bioavailability test] 4min (1)To guide drug production; (2)To guide doctor to use drug rationally, (3)To seek new drug invalid(无效)or poisoning(中毒)reasons, (4)To provide a basis in evaluating the rationality of prescription drugs. (5)To evaluate the bioequivalence of copy drug; (6)To observe the influence of food on drug absorption; (7)To observe the influence of a drug on another drug absorption; (8)To observe the influence of age or disease on drug absorption; (9)To evaluate the first effect of drugs; (10)To observe drug interactions. 6

安徽医科大学国际教育学院教案与讲稿 6 person, whose liver or kidney is disfunctional, or cardiopulmonary function is not complete. Children, pregnant or lactation women and the person with drug allergy. [Assessment of response] 2min There are 4 grades: cure or clinical relief, excellence, improvement, failure. Efficient (%) : the number of (cure + excellence)/the number of total cases*100% Some individual cases, which can't be evaluated, should be listed. [Adverse reaction evaluation ] 3min Adverse reactions includes clinical and laboratory abnormal reaction. Three type, namely A, B and C. Type A reaction： strong pharmacological function drug or the interaction with other drugs. Type A response could be observed or examined in clinical trials. Type B reaction, can be life-threatening and can't be predicted. Once happen, should be reported immediately to the organizer and drug management department. Type C reaction often appears with disease, and is not found or perceived in drugs trials, and is found through the epidemiological study. [Phase III clinical trial] 2min Phase III clinical trial is the stage for confirmation effect. Its purpose： to test the effect and safety of drug further, to provide adequate basis for drug registration eventually. Generally, phase III clinical trial should be random, blinded and controlled trial with sufficient sample size. [Phase IV clinical trial] 3min Phase IV clinical trial is the clinical trials of postmarketing, namely postmarketing surveillance. Its purpose is: (1)To investigate the curative effect and adverse reaction under the condition of widespread administration; (2) To evaluate the relationship between benefits and risks; (3) To improve administration dosage; (4) To know of the response, indications and adverse reaction further, (5) To guide clinical rational drug administration. [Drug bioequivalence test-The purpose and significance of bioavailability test] 4min (1) To guide drug production; (2) To guide doctor to use drug rationally; (3) To seek new drug invalid（无效） or poisoning （中毒）reasons; (4) To provide a basis in evaluating the rationality of prescription drugs. (5) To evaluate the bioequivalence of copy drug; (6) To observe the influence of food on drug absorption; (7) To observe the influence of a drug on another drug absorption; (8) To observe the influence of age or disease on drug absorption; (9) To evaluate the first effect of drugs; (10) To observe drug interactions