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Chapter 16-1. Pharmacology(PK/PD)

Recommended Reading : 【Chemistry】 Lecture 16. Reaction Kinetics, 【Biology】 Lecture 37. Biology Experiments


1. Overview

2. Pharmacodynamics

3. Pharmacokinetics

4. Clinical Trials


a. Drug Synergy Modeling

b. Drug Library

c. Drug Class Library



1. Overview

⑴ Pharmacology : Biochemistry that studies drugs and the body’s response to their administration.

⑵ Differences between Pharmacodynamics and Pharmacokinetics

① Pharmacodynamics : Related to receptors, ion channels, enzymes, immune system, etc.

② Pharmacokinetics : Related to absorption, distribution, metabolism, and excretion.

○ The four aspects above are collectively referred to as ADME.



2. Pharmacodynamics (PD)

⑴ Overview

① Definition : Related to receptors, ion channels, enzymes, immune system, etc.

② Tests on pharmacodynamics are mainly conducted in Phase 1 clinical trials to observe enzyme inhibitors or drug activity.

Constant 1. Ki (inhibition constant)

Michaelis-Menten Equation

Inhibitors and Reaction Kinetics

Constant 2. Kd (dissociation constant)

① Definition : The equilibrium constant for dissociation reactions; the larger the Kd, the more dissociation occurs.

② Kd is more commonly used than Ki because it can be easily determined through graphs.

③ Relationship formula


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④ Graph interpretation : When [R·L] / [R]T is 0.5, the ligand concentration [L] corresponds to Kd.


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Figure 1. Interpretation of the graph for Kd.


Constant 3. Bmax

① Total concentration of receptors.

② Unit : ligand bound / mg protein.

Constant 4. IC50

① IC50 : The inhibitor concentration at which 50% of the original ligand can dissociate.

○ Competitive binding : Treating receptors with a fixed concentration of hot ligand first, followed by varying concentrations of cold ligand to observe hot ligand dissociation.

② Dose-response curve (DRC).


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Figure 2. Dose-response curve and IC50.


③ Cheng-Prusoff Equation : Given fixed ligand concentration [L] and Michaelis constant Km.


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Constant 5. LC50

① Dose-response curve.


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Figure 3. Dose-response curve and LC50.



3. Pharmacokinetics (PK)

⑴ Definition : Related to absorption, distribution, metabolism, and excretion.

① These four aspects are collectively referred to as ADME.

② PK parameters:

○ Bioavailability F (%) = Systemic circulation dose (mg) / Administered dose (mg) × 100.

○ Absorption rate constant ka (/hr) = Systemic circulation rate (mg/hr) / Residual amount at absorption site (mg).

○ Volume of distribution Vd (L) = Amount in body (mg) / Plasma concentration (mg/L).

○ Clearance CL (L/hr) = Elimination rate (mg/hr) / Plasma concentration (mg/L).

Model 1. Monoexponential Model

① Graph : Corresponds to the first-order reaction in reaction kinetics.


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Figure 4. Monoexponential Model.


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○ AUC (area under the curve).

○ Elimination rate k is defined as follows.


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○ Doubling the initial dose : Half-life remains constant, and the time in the body increases only by one half-life.

② Steady state through chronic dosing.

○ It takes approximately five half-lives to reach steady state.


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Figure 5. Steady state through chronic dosing.


○ Loading dose : Increasing the initial dose to reach steady state faster. Important for long half-life cases.


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Figure 6. Concept of loading dose.


Model 2. Multicompartment Model

① Graph.


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Figure 7. Graph of the multicompartment model.


② Explanation of each phase:

Phase 1. Absorption phase.

○ Oxidation, reduction occur to activate the drug upon initial intake.

○ Sulfation, glucuronidation, acetylation occur to inactivate the drug for excretion.

Phase 2. Postabsorption phase (distribution phase).

Phase 3. Elimination phase.

○ Cmax, tmax (time at Cmax).


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Figure 8. Three phases of the multicompartment model.


③ ABC (accelerated blood clearance).

○ Definition : A phenomenon where drugs are rapidly excreted initially, followed by slower excretion.

IgM antibody is known to be involved in the ABC phenomenon of nanodrugs.

⑷ Pharmacokinetic experiments.

① If not completely excreted through urine, it can be interpreted as accumulating in the body.

② If not largely converted into metabolites, it can be interpreted as low bioavailability.

③ If AUCs of oral and IV administration are nearly identical, it can be interpreted as high absorption and hydrophilicity.

④ In oncology research, a tumor-to-liver ratio of 0.5 or higher indicates good pharmacokinetic properties.

4. Clinical Trials

⑴ Overview.

① Drug development stages:

○ Drug discovery : 3–5 years.

○ Preclinical : 1–2 years.

○ Clinical trials : 6–7 years.

○ FDA approval : 1–2 years.

② About 50–60 new drugs are approved by the FDA each year.

③ Costs are increasing, and failure rates are as high as 90%.

④ Most failures are due to lack of therapeutic effects.

○ Efforts are being made in Phase 1 to find efficacy and dose.

○ Phase 0 studies are introduced to test on humans earlier.

○ PET imaging is a possible strategy.

Phase 1 Clinical Trial : Exploratory clinical trial.

① Involving about 20–80 people.

Type 1. Conducted on healthy volunteers for safety assessment.

Type 2. Anti-cancer drugs : Tested on a few volunteers with terminal cancer, etc.

④ Objectives:

○ Pharmacokinetics (PK) : Theories on ADME.

○ Interaction.

○ Safety (dose-dependent).

○ MTD (maximum tolerated dose), tolerable dose range, dose-tolerance study.

○ PK / PD study.

⑤ Methods:

○ Dose-response curve : NOAEL, NOEL, MED (minimum effective dose), MABEL.

○ Single dose rising, multiple dose rising.

○ Drug-drug interaction.

Phase 2 Clinical Trial : Tested on more people; exploratory clinical trial.

① Involving about 100–200 people.

② Early Phase 2 (IIa) : Efficacy testing.

③ Late Phase 2 (IIb) : Dose finding.

Phase 3 Clinical Trial : Final stage of clinical trials for market approval; confirmatory trial.

① Conducted on a large scale for statistical confirmation.

② Objectives : Confirmation of safety and therapeutic effect.

③ Typically takes 5–6 years to obtain market approval (long-term).

Phase 4 Clinical Trial : Long-term evaluation of efficacy and safety after new drug marketing.

① Post-marketing surveillance.



Input: 2022.04.22 12:07

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