Pharmacokinetics and Pharmacodynamics

Cellular and molecular biology, Biochemistry, Organic Chemistry

The contents related to modules 1-3 leverage fundamental knowledge in Pharmacokinetics and

Pharmacodynamics (PK/PD), which is applied to solving real cases, fostering analytical and critical thinking

skills. Modules 4-5 advocate for the objective application of knowledge in more complex situations,

encouraging the development of practical PK/PD competencies. The selected teaching methodologies (TM)

combine strategies of pedagogical innovation through active learning moments, centered on the student,

aiming to promote the trilogy of knowledge in its dimensions of knowing (knowledge), doing (skills), and

being (competences):

TM1 – Interactive expository teaching through suitable audiovisual means, with active moments of

individual learning focused on solving PK/PD problems for knowledge application: Mentimeter Platform

(Worlcloud, Q&A, Multiple Choice, Ranking tools)

TM2 – Interactive expository teaching through audiovisual means with active group learning moments

centered on the analysis and discussion of PK/PD scientific articles for knowledge application: Jigsaw

Activities

TM3 – Teaching based on technical planning and execution: practice is action-oriented with the

development of skills in the analysis and resolution of practical PK/PD cases in a real context

TM4 – Problem-Based Learning (PBL): practice is action-oriented with the development of skills in the

analysis and resolution of practical PK/PD cases, using online available software

TM5 – Project-Based Learning: practice is action-oriented with the development of skills in the analysis and

formulation of BD/BE protocols

TM6 – Teaching based on planning and resolution: practice is action-oriented with the development of skills

in the analysis and resolution of practical PK/PD cases according to current regulatory guidelines

Structured knowledge of theoretical principles of pharmacokinetics and pharmacodynamics, complemented

by a practical plan for the integrated resolution of problems of increasing complexity, promotes the

articulation of content with related curriculum units (e.g., Pharmacology I, Pharmacology II).

By the end of the course unit, students are expected to have acquired skills to:

C1 – Calculate pharmacokinetic parameters that enable understanding of therapeutic inequivalence issues of medications.

C2 – Predict the kinetics and extent of the ADME process of drugs based on physicochemical, biochemical, physiological, and pathological variables.

C3 – Establish and optimize dosage regimens.

C4 – Apply appropriate protocols for assessing availability and recognize the pharmacotherapeutic consequences of its modification.

C5 – Distinguish between various equivalences and master the rules for medication substitution.

C6 – Understand the biochemical determinants of molecular targets for drugs and their fundamental pharmacodynamic concepts.

C7 – Identify drug interactions of pharmacokinetic and pharmacodynamic nature.

C8 – Articulate integrate problem-solving skills, introducing methodologies of systemic and collaborative thinking in Pharmacokinetics and Pharmacodynamics.

Module 1. L.A.D.M.E. Series (20h T)

1.1. Biopharmaceutical Classification System (BCS): solubility/permeability and BCS Classes I, II, III, and IV

1.2. Immediate-release, prolonged-release, and/or controlled-release dosage forms

1.3. Dissolution calculation: Noyes-Whitney equation

1.4. Absorption

1.4.1. Sites of drug absorption

1.4.2. Mechanisms of transmembrane passage

1.4.3. Membrane drug transporters: ABC and SLC

1.4.3. First-pass effect and presystemic degradation of the active substance

1.4.4. Factors influencing absorption

1.5. Distribution

1.5.1. Distribution within the vascular space

1.5.1.1. Plasma binding proteins

1.5.1.2. Free and bound fractions

1.5.1.3. Factors influencing variation in plasma protein binding

1.5.2. Tissue distribution

1.5.2.1. Aspects of distribution rate: effects of blood perfusion

1.5.2.2. Aspects of distribution rate: effects of diffusion rate

1.5.2.3. Aspects of the extent of tissue distribution

1.5.3. Apparent volumes of distribution

1.6. Metabolism

1.6.1. Phase 1 reactions

1.6.2. Phase 2 reactions

1.6.3. Multiplicity and isomerism of cytochrome P450

1.6.4. Drugs with high and low hepatic extraction ratios

1.6.5. Inducers and inhibitors of metabolizing enzymes

1.6.6. Metabolism kinetics

1.6.1. Single dose: determination of the rate-limiting step

1.6.2. Multiple doses: steady-state and accumulation effect

1.6.3. Factors likely to modify the kinetic profile

1.7. Elimination

1.7.1. Elimination rate constant

1.7.2. Half-life

1.7.3. Concept of clearance

1.7.4. Renal excretion

1.7.5. Biliary excretion and enterohepatic cycling

1.7.6. Other routes of excretion

1.8. Dosage: administration of single and multiple doses—loading and maintenance doses

1.9. Bioavailability

1.9.1. Absolute bioavailability

1.9.2. Relative bioavailability

1.9.3. Methods for determining bioavailability

1.9.4. Pharmacotherapeutic consequences of changes in bioavailability or bio-inequivalence: single and

multiple doses

1.9.5. Rules to follow when substituting medicines

1.9.5.1. Pharmacological equivalence

1.9.5.2. Chemical equivalence

1.9.5.3. Pharmaceutical equivalence

1.9.5.4. Biological equivalence or bioequivalence

1.9.5.5. Clinical or therapeutic equivalence

1.10. Chronopharmacokinetics and special situations

1.11. Pharmacokinetic interactions

Module 2. Pharmacodynmics (10h T)

2.1. Molecular targets of drugs:

2.1.1. Ionotropic receptors: blockers and allosteric modulators

2.1.2. Metabotropic receptors

2.1.3. Receptors with intrinsic kinase activity or kinase-coupled receptors

2.1.4. Nuclear receptors

2.1.5. Post-translational modifications of receptors and macromolecular complexes

2.1.6. Enzymes: inhibitors, false substrates, prodrugs, and cofactors

2.1.7. Transporters: inhibitors and false substrates

2.1.8. Desensitization, tolerance, and resistance

2.2. Dose-response curves (full agonists, partial agonists, inverse agonists, and antagonists)

2.3. Definition of specificity, affinity, intrinsic efficacy, and potency

2.4. Types of concentration–pharmacological effect relationships

2.4.1. Indirect effects

2.4.2. Irreversible effects

2.4.3. Direct reversible effects

2.5. Application of receptor theory and the Hill equation

2.6. Pharmacodynamic interactions

Practical matrix (P)

Module 1. Basic Mathematical Concepts for Biopharmaceutics and Pharmacokinetics (8h P)

1.1. Exponents and logarithms

1.2. Calculation of area under the curve (AUC): concepts of differential and integral calculus applied to the

evaluation of absorption and disposition phenomena

1.3. Calculation of mean residence time (MRT), mean dissolution time (MDT), and mean absorption time

(MAT)

1.4. Mathematical and graphical expressions of reaction rates: zero-order and first-order reactions

1.5. Equations for describing linear, nonlinear, and compartmental pharmacokinetic models

1.6. Units used to express drug concentrations

Module 2. Practical Cases for Problem-Based Learning (12h P)

2.1. Determination of systemic, hepatic, and intrinsic clearance

2.2. Determination of hepatic extraction ratio

2.3. Determination of kinetic parameters associated with bioavailability

2.4. Comparison of pharmacokinetic profiles and parameters in different study situations related to

bioavailability

Module 3. Bioequivalence Research Protocols and Current EMA Guidelines (10h P)

3.1. Guidelines for bioequivalence studies (EMA)

3.2. Establishment of a bioavailability protocol:

3.2.1. Sampling selection

3.2.2. Assay methods: carryover effect and washout period

3.2.3. Experimental conditions—sampling frequency, sampling duration, crossover or non-crossover design,

randomization, statistical analysis, dosing schedule, selection of reference formulation, food intake, and

bioavailability study

NAO