Kinetics

Introduction to Biopharmaceutics and Pharmacokinetics

Overview of the Course

  • Course Title: PSW 313: Biopharmaceutics/ Pharmacokinetics

  • Instructor: Dr. G. Acquaah-Mensah

  • Lecture Focus: Introduction to Biopharmaceutics and Pharmacokinetics

Course Objectives

  • Pharmacokinetics in Pharmacotherapy: Understanding the role of pharmacokinetics in effective drug therapy.

  • Definitions: Defining key terms associated with pharmacokinetics, biopharmaceutics, and pharmacodynamics.

  • Assay Techniques: Discussing various approaches to assaying biological specimens related to drug studies.

  • Models: Explaining pharmacokinetic models and their applications.

  • Model Distinctions: Distinguishing between various types of pharmacokinetic models.

Pharmacists' Patient Care Process

The Role of Pharmacists

  • Pharmacists are recognized as medication experts and integral members of the health care team.

  • They employ a person-centered approach to enhance medication efficacy and achieve optimal health outcomes.

Five Steps of Patient Care Process

  1. Collect: Gathering subjective and objective information about the patient, including medical and medication history. Information is verified from various sources: patients, caregivers, health records, and other health professionals.

  2. Assess: Evaluating the collected information to determine and prioritize patient needs. This assessment aids in formulating a care plan.

  3. Plan: Developing a tailored, evidence-based, and cost-effective care plan collaboratively with the patient and/or caregiver, integrating the roles of other healthcare team members.

  4. Implement: Executing the care plan in coordination with the patient and the healthcare team, ensuring that it is prioritized appropriately based on patient needs.

  5. Follow Up/Monitor and Evaluate: Continuously following up to assess the effectiveness of the care plan and make adjustments as necessary through collaboration with the patient, caregivers, and the care team.

Introduction to Relevant Concepts

Phases of Drug Action

  • Pharmaceutical Phase: Involves drug disintegration and dissolution leading to pharmacological availability. This phase assesses how a drug becomes available at the site of action.

  • Pharmacokinetic Phase: Includes absorption, distribution, metabolism, and excretion (ADME) processes, ultimately influencing drug concentration in the body.

  • Pharmacodynamic Phase: Focuses on drug-target interactions and the resulting pharmacological effects on the body.

Biopharmaceutics

Definition

  • Biopharmaceutics: The field studying the relationship between the biological effects of drugs and their physicochemical properties. Some authorities classify pharmacokinetics as a subset of biopharmaceutics.

Factors Influencing Biopharmaceutics

  1. Drug Stability: The chemical and physical stability of the drug throughout its shelf life.

  2. Release Rate: The rate at which a drug is released from its formulation (product) and into the body (absorption site).

  3. Dissolution/Absorption Site: Rate of drug dissolution at the absorption site, which affects systemic absorption.

Formulation Properties Affecting Biopharmaceutics

  • Types of dosage form (e.g., tablets, injections).

  • Pharmaceutical processes used in preparation (e.g., mixing, coating).

  • Presence/absence of adjuncts (substances added to enhance drugs).

  • Physical characteristics (e.g., particle size, surface area).

  • Chemical nature (e.g., the form of the drug: salt, complex, ester).

Pharmacokinetics

Definition

  • Pharmacokinetics: Derived from Greek terms 'pharmakon' (drug) and 'kinetos' (motion), it encompasses the mathematical analysis of the ADME time courses, examining how drugs are absorbed, distributed, metabolized, and eliminated.

Key Parameters in Pharmacokinetics

  • Amount of Drug Administered: Total drug given in a dosage form.

  • Amount of Drug in Body: Drug levels present in the systemic circulation.

  • Amount of Drug Eliminated: Amount of drug cleared from the body.

  • Rate Constant for Absorption: Indicates how quickly a drug is absorbed into the systemic circulation.

  • Rate Constant for Elimination: Represents how quickly a drug is removed from the body.

Experimental Aspects of Pharmacokinetics

  • Biologic Sampling Techniques: Development of methods to collect biological samples for analysis.

  • Assay Methods: Techniques for measuring drug concentrations and metabolites.

  • Data Collection and Manipulation: Approaches for efficient data handling and interpretation.

Theoretical Aspects of Pharmacokinetics

  • Models are employed to predict drug absorption, distribution, metabolism, and excretion after administration.

  • Classical Pharmacokinetics: Focused on model development and estimation of parameters.

Clinical Aspects of Pharmacokinetics

  • Consideration of patient-specific factors when optimizing dosing strategies.

  • Therapeutic Drug Monitoring (TDM) for drugs with a narrow therapeutic index (e.g., warfarin).

  • Population Pharmacokinetics: Considering variations in pharmacokinetics across different demographics (age, gender, ethnicity, genetics).

Relationship of Drug Concentrations to Drug Response

  • Graphical representation indicates various levels of drug concentration:

    • Toxic: Concentrations leading to adverse effects.

    • Restorative: Therapeutic concentrations.

    • Subtherapeutic: Levels not achieving the desired therapeutic effect.

Toxicokinetics

Definition

  • Toxicokinetics: The application of pharmacokinetic principles to toxicology, specifically in interpreting pre-clinical toxicity and predicting effects in humans.

  • Focus on non-linear pharmacokinetics at high doses, leading to saturation of enzymes and related processes.

Pharmacodynamics

Definition

  • Pharmacodynamics: The study of the relationship between drug concentration at the site of action and the pharmacologic response, essentially answering, “What the drug does to the body.”

Drug Concentration Assays

Biological Specimens

  • Various types of biological specimens analyzed include blood concentrations, tissue concentrations, and other body fluids, with notable applications in therapeutics and forensic science.

Obtaining Biological Specimens

  • Invasive Methods: Require surgical or parenteral intervention, e.g., blood or tissue biopsies.

  • Non-Invasive Methods: Include saliva, urine, feces, and expired air for sample collection.

Assay Types

  • Chromatography (e.g., HPLC): Separates drugs from other substances.

  • Immunoassays: Utilize specific reactions between antigens and antibodies (e.g., fluorescence assays).

  • Radioactive Assays: Detect radioactively labeled drugs (e.g., TCA-RA assay).

  • Mass Spectroscopy: Analytical technique for identifying compounds.

Data from Biological Specimens

  • Provide insights into pharmacologic/toxicologic outcomes, metabolite formation, and the quantity of drug transported to specific tissues.

Plasma Concentration-Time Course

Key Terms and Concepts

  • AUC (Area Under the Curve): Represents total drug exposure over time. Important for studying toxicity and bioequivalence.

  • Minimum Effective Concentration: The lowest drug concentration needed to achieve a desired therapeutic effect.

  • Minimum Toxic Concentration: The concentration that yields adverse toxic effects.

Plasma Concentration-Time Course Analysis

  • Evaluates drug exposure, onset of action, peak concentration, and peak time following oral drug administration.

Use of Plasma Concentrations in Clinical Settings

  • Optimizing dosage regimens based on individual plasma concentration data, integrating pharmacodynamic responses where necessary.

Tissue Concentrations

Tissue Biopsies

  • Rarely performed due to inherent variability in drug concentration across tissues and blood flow characteristics.

Urine and Fecal Concentrations

  • Urine concentration reflects systemic drug levels; fecal concentration may indicate non-absorption after administration or biliary secretion.

Saliva Concentrations

  • Saliva is a useful indicator for free drug levels in plasma, particularly when equilibrium with plasma has been established.

Pharmacokinetic Models

General Concepts

  • Model: A mathematical construct that quantifies the relationships between pharmacokinetic parameters.

  • Applications of models include: predicting drug concentrations, optimizing dosage, correlating effects, estimating accumulation, and explaining interactions.

Pharmacokinetic Parameters

  • Volume of Distribution (VD): Describes the volume in which the drug disperses within the body.

  • Elimination Rate Constant (ke): Determines the rate of drug concentration decrease.

  • Half-life (t1/2): Time needed for the drug concentration to reduce by half.

Model Types

  1. Physiologically-Based Models: Also known as blood flow models, they rely on anatomical and physiological data and offer realistic tissue distribution predictions.

  2. Compartment Models: Simplified models grouping tissues with similar characteristics. Two primary configurations:

    • Mammillary Models: Include one or multiple compartments (e.g., two-compartment model).

    • Catenary Models: Multiple interconnected compartments, resembling a chain.

Contrasting Physiological and Compartmental Models

  • Physiological models are data-driven and influenced by pathophysiology.

  • Compartment models simplify the complexities of the body into manageable constructs but may not reflect physiological realities as accurately as physiologically-based models.