《Biopharmaceutics and Pharmacokinetics》课程教学大纲（三号黑体）

一、课程基本信息

二、课程目标

（一）总体目标：

 Biopharmaceutics and Pharmacokinetics is a major required courses for pharmaceutical students. This course aims to provide professional information to students and benefit for an overall understanding of pharmaceutical science,familiar with the professional discipline knowledge, to grasp the concept of biopharmaceutics and pharmacokinetics, improve the capability to solve professional problems in drug development and pharmaceutical practices.To develop a sense of discipline identity of biopharmaceutics and pharmacokinetics, to clarify the direction and good learning objectives of future professional learning, and provide guidance for personal professional career development.

（二）课程目标：

 Biopharmaceutics and Pharmacokinetics is very important in pharmaceutical area,which is a discipline that investigates the fate of drug in the body dynamically. This course describes factors affecting the absorption, distribution, and metabolism, and excretion of drugs. The students will be able to demonstrate an understanding of the differential and integrated equations associated with pharmacokinetic models and assess factors which affect the absorption, distribution, metabolism and excretion of drugs. At the same time, they will be able to describe the techniques used to determine drug concentrations in biological and formulation matrices and calculate appropriate dosing regimens using appropriate criteria.

课程目标1：(chapter 1,2,4,5,6,7，8,9,10）

1.1 Master the definition of pharmacokinetics, research contents and basic pharmacokinetic parameters, grasp the calculation methods of pharmacokinetic parameters for different administration routes of one-compartment model. Understand the blood drug concentration-time curve and estimation of pharmacokinetic parameters of multi-compartment model, familiar with to identify compartment model. Master the basic concepts related to multi-dose administration, drug accumulation and blood concentration fluctuation.

1.2 Master the characteristics of nonlinear pharmacokinetics and Michaelis–Menten kinetics equation, approach the basic concept of statistical moment and the estimation of pharmacokinetic parameters.

课程目标2：(chapter 11,12,14，15，16）

 2.1 Understand the significance of biopharmaceutics and pharmacokinetics to new drug research and development and clinical application.

 2.2 Master the structure and properties of biofilms, drug transport mechanism, drug absorption pathways in different parts, and factors affecting drug absorption including physiology, drugs, dosage forms and preparations.

 2.3 Master the basic concepts of drug distribution, excretion and metabolism;skilled with the factors that affect drug distribution, the types of drug metabolic reactions and the factors that affect drug metabolism.To master the characteristics and influencing factors of renal excretion and other excretory pathways of drugs.

2.4 Understand the application of pharmacokinetics in clinical pharmacy and new drug research and development, master the design of drug administration regimen, the detection of therapeutic drugs and the individualized design of drug administration regimen. Familiar with the research contents of new drugspharmacokinetics, the basic requirements of bioavailability, research methods and evaluation methods of bioequivalence.

（三）课程目标与毕业要求、课程内容的对应关系

表1：课程目标与课程内容、毕业要求的对应关系表

三、教学内容

第一章 Introduction to Biopharmaceutics and Pharmacokinetics

1.教学目标

(1) Understanding the definition of biopharmaceutics and pharmcokinetics, and relationship with drug product performance.

(2) Describe the role of biopharmaceutics and pharmcokinetics in a new drug development and clinical application.

2.教学重难点

(1) The definition of biopharmaceutics and pharmacokinetics.

(2) The application of biopharmaceutics and pharmacokinetics in new drug development and clinical drug application.

3.教学内容

Drug Product Performance, Biopharmaceutics, Pharmacokinetics, Pharmacodynamics, Clinical Pharmacokinetics, Measurement of Drug Concentrations, Basic Pharmacokinetics and Pharmacokinetic Models.

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom will be encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

第二章 Mathematical Fundamentals in Pharmacokinetics

1.教学目标

(1) Learn to algebraically solve mathematicalexpressions related topharmacokinetics.

(2) Express the calculated andtheoretical pharmacokineticvalues in proper units.

(3) Define various modelsrepresenting rates and orderof reactions and calculatepharmacokinetic parameters(eg, zero- and first-order) fromexperimental data based onthese models.

2.教学重难点

(1) Mathematicalexpressions related topharmacokinetics

(2) Rates and orderof reactions and calculatepharmacokinetic parameters(eg, zero- and first-order) fromexperimental data

3.教学内容

Calculus, Graphs, Mathematical Expressions and Units, Units for Expressing Blood Concentrations, Measurement and Use of Significant Figures, Rates and Orders of Processes.

 4.教学方法

 (1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

 (2) Discussion method: Flipped classroom was encouraged.

 5.教学评价

 Take quick summary test, discuss with selected learning questions and frequently asked questions.

第三章 One-Compartment Open Model: Intravenous Bolus Administration

1.教学目标

(1) Describe a one-compartmentmodel, IV bolus injection.

(2) Provide the pharmacokineticterms that describe a onecompartment model, IV bolusinjection, and the underlyingassumptions.

(3) Explain how drugs follow onecompartment kinetics usingdrug examples that follow onecompartment kinetics.

(4) Calculate pharmacokineticparameters from drugconcentration–time data using aone-compartment model.

(5) Calculate the IV bolus doseof a drug using the onecompartment model equation.

2.教学重难点

(1) The definition of pharmacokinetic compartment model,the significance of one compartment model for intravenous bolus administration.

(2) The calculation of pharmacokinetic parameters.

3.教学内容

Elimination rate constant, apparent volume of distribution, clearance, clinical application, calculation of k from urinary excretion data.

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom was encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

第四章 Multicompartment Models: Intravenous Bolus Administration

1.教学目标

(1) Define the pharmacokineticterms used in a two- and threecompartment model.

(2) Explain using examples whydrugs follow one-compartment,two-compartment, or threecompartment kinetics.

(3) Use equations and graphto simulate plasma drugconcentration at varioustime periods after an IV bolusinjection of a drug that followsthe pharmacokinetics of a twoand three-compartment modeldrug.

(4) Estimate two-compartmentmodel parameters by using themethod of residuals.

2.教学重难点

Whydrugs follow one-compartment,two-compartment, or threecompartment kinetics, estimate two-compartmentmodel parameters by using themethod of residuals.

3.教学内容

Two-Compartment Open Model, Clinical Application, Three-Compartment Open Model, Determination of Compartment Models, Practical Problem

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom was encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

第五章 Intravenous Infusion

1.教学目标

(1) Describe the concept of steadystate and how it relates tocontinuous dosing.

(2) Determine optimum dosing foran infused drug by calculatingpharmacokinetic parametersfrom clinical data.

(3) Calculate loading doses tobe used with an intravenousinfusion.

(4) Describe the purpose of aloading dose.

2.教学重难点

Pharmacokinetic parameters for one-compartment model drugs after intravenous infusion, loading dose,estimation of drug clearance and V_D.

3.教学内容

One-compartment model drugs, infusion method for calculating patient elimination half-life,loading dose plus iv infusion-one-compartment model,estimation of drug clearance and V_D from infusion data.

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom was encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

第六章 Drug Elimination, Clearance, and Renal Clearance

1.教学目标

(1) Describe the main routes of drugelimination from the body.

(2) Understand the importanceof the role of clearance as a PKparameter.

(3) Define clearance and itsrelationship to a correspondinghalf-life and a volume ofdistribution, differentiate between clearanceand renal clearance.

2.教学重难点

The definition and significance of drug elimination, clearance, renal clearance, determination of renal clearance, relationship of clearance to elimination half-life and volume of distribution.

3.教学内容

Drug elimination, drug clearance, clearance models, the kidney, renal clearance, determination of renal clearance, relationship of clearance to elimination half-life and volume of distribution.

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom was encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

第七章 Pharmacokinetics of Oral Absorption

1.教学目标

(1) Define oral drug absorptionand describe the absorptionprocess.

(2) Introduce two generalapproaches used for studyingabsorption kinetics and theirsimilarities and differences.

(3) Understand the basic principlesfor physiologically basedabsorption kinetics.

(4) Describe the oral onecompartment model andexplain how this modelsimulates drug absorption fromthe gastrointestinal tract.

(5) Calculate the pharmacokineticparameters of a drugthat follows the oral onecompartment model, the fraction of drugabsorbed in a one-compartmentmodel using the Wagner–Nelsonmethod.

2.教学重难点

Understand the oral drug absorption principles and process, the basic principles for physiologically based absorption kinetics, calculate the pharmacokinetic parameters of a drug that follows the oral one compartment model.

3.教学内容

Basic principles of physiologically based absorption kinetics (bottom-up approach), absorption kinetics (the top-down approach), pharmacokinetics of drug absorption, significance of absorption rate constants, zero-order absorption model, first-order absorption model.

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom was encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

第八章 Multiple-Dosage Regimens

1.教学目标

(1) Define drug accumulation, accumulation index and drug accumulation t_1/2.

(2) Explain the principle ofsuperposition and itsassumptions in multiple-doseregimens.

(3) Calculate the steady-state C_maxand C_min after multiple IV bolusdosing of drugs, k and V_D ofaminoglycosides in multiple-dose regimens.

2.教学重难点

The definition of drug accumulation and evaluate related pharmacokinetic parameters.  

3.教学内容

Drug accumulation, repetitive intravenous injections, intermittent intravenous infusion, estimation of k and V_D of aminoglycosides in clinical situations, multiple-oral-dose regimen, loading dose, dosage regimen schedules.

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom was encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

第九章 Nonlinear Pharmacokinetics

1.教学目标

(1) Describe the differences betweenlinear pharmacokinetics andnonlinear pharmacokinetics.

(2) Explain how to detect nonlinearkinetics using AUC­versus­dosesplots.

(3) Learn to apply Michaelis–Menten equation and graphical methods to calculateV_max and K_M.

2.教学重难点

The necessity to study Nonlinear Pharmacokinetics, how to determine Nonlinear Pharmacokinetics, the properties of Nonlinear Pharmacokinetics, calculation of related PK parameters.

3.教学内容

Saturable Enzymatic Elimination Processes, Drug Elimination by Capacity-Limited Pharmacokinetics: One-Compartment Model, IV Bolus Injection, drugs distributed as one-compartment model and eliminated by nonlinear pharmacokinetics, chronopharmacokinetics and time-dependent pharmacokinetics, bioavailability of drugs that follow nonlinear pharmacokinetics, nonlinear pharmacokinetics due to drug–protein binding, potential reasons for unsuspected nonlinearity, dose-dependent pharmacokinetics.

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom was encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

第十章 Physiologic Drug Distribution and Protein Binding

1.教学目标

(1) Describe the physiology of drugdistribution in the body.

(2) Explain how drug distribution isaffected by blood flow, protein,and tissue binding.

(3) Describe how drug distributioncan affect the apparent volumeof distribution.

(4) Explain how volume ofdistribution, drug clearance,and half-life can be affected by

 protein binding.

2.教学重难点

The physiology of drugdistribution in the body, factors affect drug distribution, the definition and significance of drug protein binding in vivo, the relationship between drug distribution, drug clearance and half-life of elimination.

3.教学内容

Physiologic factors of distribution, apparent volume distribution, protein binding of drugs, effect of protein binding on the apparent volume of distribution, relationship of plasma drug–protein binding to distribution and elimination, determinants of protein binding, kinetics of protein binding.

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom was encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

第十一章 Drug Elimination and Hepatic Clearance

1.教学目标

(1) Describe the pathways for drugelimination in the body.

(2) Describe the role of hepaticblood flow, drug proteinbinding, and intrinsic clearanceon hepatic clearance.

(3) Describe the biotransformationof drugs in the liver and whichenzymatic processes areconsidered “phase I reactions”and “phase II reactions.”

2.教学重难点

Understanding the definition of drug Drug Elimination and Hepatic Clearance, factors affecting Drug Elimination, biotransformation pathway of drug in vivo.

3.教学内容

Route of drug administration and extrahepatic drug metabolism, hepatic clearance, extrahepatic metabolism, enzyme kinetics, anatomy and physiology of the liver, hepatic enzymes involved in the biotransformation of drugs, drug biotransformation reactions, pathways of drug biotransformation, biliary excretion of drugs, role of transporters on hepatic clearance and bioavailability.

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom was encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

第十二章 Physiologic Factors Related to Drug Absorption

1.教学目标

(1) Define passive , active drugabsorption, transcellular andparacellular drug absorption.

(2) Explain how Fisk's law ofdiffusion relates to passive drugabsorption.

(3) Calculate the percent of drugnonionized and ionized fora weak acid or weak-basedrug using the Henderson–Hasselbalch equation, andexplain how this may affect drugabsorption.

(4) Describe the anatomy andphysiology of the GI tract andexplain how stomach emptyingtime and GI transit time canalter the rate and extent of drugabsorption.

(5) Explain the effect of food ongastrointestinal physiology andsystemic drug absorption.

(6) Describe the varioustransporters and how theyinfluence the pharmacokineticsof drug disposition in the GI tract

(7) Explain the pH-partitionhypothesis and howgastrointestinal pH and the pKaof a drug may influence systemicdrug absorption. Describe howdrug absorption may be affectedby a disease that causes changesin intestinal blood flow and/ormotility.

(8 )List the major factors thataffect drug absorption fromoral and non-oral routes of drugadministration.

2.教学重难点

Understanding the mechanisms of drug absorption, the anatomy and physiology drug absorption organs, the physicochemical and physiological factors influencing drug absorption, important equations to describe the absorption.

3.教学内容

Drug absorption and design of a drug product, route of drug administration, nature of cell membranes, passage of drugs across cell membranes, drug interactions in the gastrointestinal tract, oral drug absorption, oral drug absorption during drug product development, methods for studying factors that affect drug absorption, effect of disease states on drug absorption, miscellaneous routes of drug administration.

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom was encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

第十三章 Biopharmaceutic Considerations in Drug Product Design and In Vitro Drug Product Performance

1.教学目标

(1) Describe the biopharmaceuticfactors affecting drug design.

(2) Differentiate between the termssolubility and dissolution, drug absorption andbioavailability,

(3) Describe the various in vitro andin vivo tests commonly used toevaluate drug products.

(4) Define in vitro–in vivo correlation(IVIVC) and explain why aLevel A correlation is the mostimportant correlation for IVIVC

(5) Explain the biopharmaceuticclassification system andhow solubility, dissolution,and permeation apply to BCSclassification.

2.教学重难点

Understanding the biopharmaceuticfactors affecting drug design, the significance and method to estimate in vitro–in vivo correlation(IVIVC),the biopharmaceuticclassification system andhow solubility, dissolution,and permeation apply to BCSclassification.

3.教学内容

Biopharmaceutic factors and rationale for drug product design, rate-limiting steps in drug absorption, physicochemical properties of the drug, formulation factors affecting drug product performance, drug product performance, in vitro: Dissolution and drug release testing, compendial methods of dissolution, dissolution profile comparisons, problems of variable control in dissolution testing, performance of drug products: In vitro–in vivo correlation, drug product stability, considerations in the design of a drug product.

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom was encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

第十四章 Drug Product Performance, In Vivo: Bioavailability and Bioequivalence

1.教学目标

(1) Define bioavailability,bioequivalence, and drugproduct performance.

(2) Explain why certain drugsand drug products have lowbioavailability.

(3) Explain why first-pass effect aswell as chemical instability of adrug can result in low relativebioavailability.

(4) Describe various methodsfor measuring bioavailabilityand the advantages anddisadvantages of each.

2.教学重难点

Understanding the difference between bioavailability and bioequivalence, and how these parameters influence drugproduct performance and development.

3.教学内容

Drug Product Performance, Purpose of Bioavailability and Bioequivalence Studies, Relative and Absolute Availability, Methods for Assessing Bioavailability and Bioequivalence, In Vivo Measurement of Active Moiety or Moieties in Biological Fluids, In Vitro Studies, Bioequivalence Studies, Design and Evaluation of Bioequivalence Studies, The Biopharmaceutics Classification System (BCS), Special Concerns in Bioavailability and Bioequivalence Studies.

4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework, combined with typical drug examples.

(2) Discussion method: Flipped classroom was encouraged.

5.教学评价

Take quick summary test, discuss with selected learning questions and frequently asked questions.

四、学时分配

表2：各章节的具体内容和学时分配表

五、教学进度

表3：教学进度表

六、教材及参考书目

 1. 刘建平主编，生物药剂学与药物动力学，人民卫生出版社，2016年

2. Patrick J. Sinko，Martin’s Physical Pharmacy and Pharmaceutical Sciences，Wolters Kluwer，2011年.

3. 方亮主编，药剂学，人民卫生出版社，2016年

 4. Alexander T Florence, Physicochemical Principles of Pharmacy，Pharmaceutical Press，2006年.

七、教学方法

 1. Teaching method: Teaching the basic concepts and principles of this course by PPT and video, etc.,promote the students can understand the relevant professional knowledge of pharmaceutical science.

 2.Discussing method: The heuristic teaching method will be employed in the class, and flipping classroom will be used at regular intervals to encourage the active studying and learning presentation techniques, too.

八、考核方式及评定方法

（一）课程考核与课程目标的对应关系

表4：课程考核与课程目标的对应关系表

（二）评定方法

1．评定方法

（例：平时成绩：10%，期中考试：30%，期末考试60%，按课程考核实际情况描述）

2．课程目标的考核占比与达成度分析

表5：课程目标的考核占比与达成度分析表

（三）评分标准