Untitled

PHARMA BIOPHARMACEUTICS & PHARMACOKINETICS NOTES

Institution Details

  • University: Our Lady of Fatima University - College of Pharmacy

  • Year Established: 1967

  • Author: Mariel Nina M. Esguerra

OLFU Vision

  • Vision Statement: A premier inclusive university of choice aspiring to improve man as man by developing individuals through a legacy of excellent education and compassionate value formation.

  • Goals of OLFU:

    • Commitment to societal service through quality education.

    • Development of individual capabilities to maximize potential.

    • Nurturing future professionals with solid academic foundations and skills to become leaders in society.

    • Responding effectively to the changing needs through continued professional education and research.

    • Inculcating social awareness through community outreach.

    • Instilling environmental awareness for the protection of national and global resources.

    • Fostering a deep sense of nationalism and pride in Filipino heritage.

    • Upholding virtues of truth, justice, integrity, compassion, and faith in God.

Graduate Attributes

  • Desired Attributes:

    • Aspirational

    • Compassionate

    • Honorable

    • Inspiring

    • Ethical

    • Visionary

    • Efficient

    • Responsible

University Core Values

  • Core Values:

    • Respect

    • Integrity

    • Service

    • Excellence

College of Pharmacy Mission and Vision

  • Mission Statement: Committed to preparing students to be ethically competent, professionally competent, research-oriented, service-oriented, and environment-conscious pharmacy professionals.

  • Vision: To become a top-notch provider of excellent education for future pharmacy professionals through adherence to current industry standards.

Course Details

  • Course Code: PHBP 221

  • Credit Units: 3 units lecture

  • Prerequisite/Co-requisite: Physical Pharmacy

  • Placement: Second Year, 1st Semester

Course Description

  • This course involves the study of intrinsic, formulation, physiologic, and pathologic factors affecting the bioavailability of drugs from drug products. The focus includes drug absorption, distribution, metabolism, excretion, and how these processes are influenced by varying factors affecting drug presence and action in biological systems.

Grading System

  • Assessment Breakdown:

    • Prelim Exam: 20%

    • Midterm Exam: 20%

    • Final Exam: 20%

    • Quizzes: 30%

    • Assignments: 5%

    • Attendance: 5%

Unit Outcomes

  • By the end of this module, students are expected to:

    1. Define Biopharmaceutics & Pharmacokinetics

    2. Define the LADMER system

    3. Describe pharmacotechnical parameters affecting liberation and discuss their clinical significance

Unit Outline

  • Key Topics:

    • Definition of Terms

    • Overview of LADMER System

    • Measurement of Drug Concentration and Its Importance

    • Physicochemical Properties Affecting Drug Absorption

    • Liberation Process

Key Definitions

Biopharmaceutics

  • Definition: The science that examines the interrelationship between the physicochemical properties of drugs, the dosage form, and the route of administration on the rate and extent of systemic drug absorption.

  • Focus Area: The study of chemical and physical properties of drugs, components, and activities in living organisms.

Pharmacokinetics

  • Definition: The study of the time course of drug movement in the body during absorption, distribution, and elimination.

Pharmacology and Its Divisions

  • Pharmacodynamics: Effects of drugs on the body.

  • Pharmacokinetics: Effects of the body on drugs.

LADMER System

  • Components:

    • L: Liberation

    • A: Absorption

    • D: Distribution

    • M: Metabolism

    • E: Excretion

    • R: Response

Liberation

  • Definition: The delivery of the active ingredient from a dosage form into solution (also known as the drug release process).

Liberation Process

  • Details:

    • It determines the onset of action, rate of absorption, and availability for all drug products, except IV and oral true solutions.

    • Controlled by drug product characteristics involving two processes: disintegration and dissolution.

Dosage Forms Affecting Liberation

  • Impacted Forms:

    • Parenteral Injections (IV, IM, ID, SC)

    • Sublingual and Buccal Tablets

    • Modified Release Dosage Forms (Extended-release, Delayed-release, Targeted release)

Absorption

  • Definition: The uptake process of a compound from the administration site into systemic circulation.

  • Key Factors:

    • Incomplete liberation leads to incomplete absorption.

    • Bioavailability (F) measures absorption rate as $F ext{-} 1 = 100 ext{% or complete absorption}$ and is less than 100% for oral administrations.

First-Pass Effect

  • Definition: A phenomenon where a drug is metabolized in a specific body location, reducing the active drug concentration upon reaching systemic circulation or action site.

Distribution

  • Definition: The transfer of the drug from the blood to extravascular fluids and tissues, influenced by blood perfusion in an area.

Metabolism

  • Definition: Detoxification or biotransformation, involving enzymatic conversion of drug substances to less toxic metabolites, promoting easier elimination.

  • Relevant Term: Xenobiotics - foreign chemicals.

Excretion

  • Definition: The final elimination of drug substance or its metabolites from the body.

    • Mechanisms of Excretion:

    • Polar metabolites: Eliminated through kidneys.

    • Non-polar drugs: Eliminated through bile.

Response

  • Definition: Referring to therapeutic outcomes including efficacy, side effects, and toxic effects of drugs.

  • Quote by Paracelsus: "All drugs are poison. It is just a matter of dose."

Important Terms and Concepts

Clinical Pharmacokinetics

  • Definition: Application of pharmacokinetic methods for drug therapy, studying relationships between dosage regimens and concentration-time profiles.

    • Parameters:

    1. Clearance: Volume of fluid cleared of drug per unit time.

    2. Volume of Distribution: Apparent volume required to contain the drug concentration observed.

    3. Elimination Half-life: Time taken for 50% of the drug to be eliminated.

Therapeutic Drug Monitoring (TDM)

  • Application: Monitoring drug levels in blood to optimize efficacy and prevent toxicity, especially for drugs with a narrow therapeutic range.

Population Pharmacokinetics

  • Definition: Studies pharmacokinetic variations based on diverse populations.

Experimental Pharmacokinetics

  • Focus: Development of biologic sampling techniques and analytical methods for measuring drugs/metabolites.

    • Types:

    • In vivo: Involving human subjects/laboratory animals.

    • In vitro: Using test apparatus with no living subjects.

Theoretical Models in Pharmacokinetics

  • Definition: Models predict drug disposition after administration.

    • Types of Models:

    1. Empirical Models: Derived equations from plasma concentration and time data.

    2. Physiological Models: Describe drug movement based on organ blood flow and spaces.

    3. Compartment Models: Grouping organs with the same blood flow and drug affinity.

Compartment Models

  • Overview: Hypothetical spaces defined by unspecified membranes for drug transfer.

    • Types:

    1. Catenary Models: Compartments joined like train cars.

    2. Mamillary Models: Peripheral compartments connected to a central compartment.

    3. Physiologic Models: Blood flow distribution.

Pharmacodynamics

  • Definition: Study of drug concentration at the site of action and its pharmacologic response.

Clinical Toxicology

  • Definition: Study of adverse effects of drugs and toxic substances.

  • Philosophical Quote: "All things are poison; nothing is without poison; only the dose makes a thing not a poison."

Measurement of Drug Concentration

  • Methods of Sampling:

    • Invasive Methods: Requires surgical or parenteral intervention (e.g., blood, spinal fluid).

    • Non-invasive Methods: Without intervention (e.g., urine, saliva).

Types of Blood Components

  • Components of Blood:

    • Whole Blood: Comprises plasma, clot, and serum.

    • Serum: Obtained post-centrifugation of clotted blood.

    • Plasma: Isolating plasma using heparin.

Importance of Measuring Plasma Drug Concentration

  • Key Aspects:

    • Adjusting drug dosage for individual optimization.

    • Monitoring disease progress.

Plasma Concentration vs. Time Curve

  • Key Components:

    • Minimum Effective Concentration (MEC): Minimal concentration for desired effects.

    • Minimum Toxic Concentration (MTC): Concentration threshold for toxicity.

    • Onset Time: Time to reach MEC.

    • Peak Time: Time of maximum drug concentration.

    • AUC (Area Under Curve): Total drug absorbed systematically.

Areas Related to Drug Absorption

  • Influential Factors:

    • Rate of dissolution and solubility are crucial to bioavailability.

    • Various physicochemical properties profoundly influence dissolution and absorption, including particle size, partition coefficient, salt formation, and more.

Drug Dissolution and Solubility

  • Key Concepts:

    • Rate-limiting step in bioavailability often determined by the drug dissolution rate.

    • The Noyes-Whitney equation plays a role in controlling drug dissolution.

Physicochemical Properties

  • Factors influencing drug design and release include:

    • Particle size and surface area

    • Ionization extent

    • Partition coefficients

Extent of Ionization

  • Defined by the Henderson-Hasselbalch equation relating pH and pKa for weak electrolytes.

  • Ionized forms are generally more soluble, whereas non-ionized forms may have different pharmacokinetic properties.

Salt Formation

  • Weakly acidic and basic drugs form various salt types influencing their absorption and stability.

Polymorphism

  • Ability of a drug to form multiple crystalline structures affecting dissolution rates and overall bioavailability.

Chirality

  • Drugs may exist as stereoisomers with differing pharmacodynamics; the activity may vary based on enantiomeric composition.

Hydrates & Complex Formation

  • Hydrates: Varying dissolution rates between hydrated and anhydrous forms.

  • Complexes: Formations that can alter chemical properties and absorption; chelation examples include tetracycline.

Conclusion

  • Understanding the complex interrelationships in biopharmaceutics and pharmacokinetics is critical for optimizing drug design and ensuring effective therapy. The integration of physicochemical principles, clinical studies, and pharmacokinetic modeling remains foundational in pharmacy education and practice.