Intravenous Bolus Administration Study Guide

Intravenous Bolus Administration - Study Guide

• Concentration-Time Profiles: Oral drug concentration starts at zero, peaks, then declines.
• Minimum Effective Concentration (MEC): Drug concentration for a response.
• Maximum Therapeutic Concentration (MTC): Concentration above which toxicity is likely.
• Therapeutic Window: The safe and effective concentration range (MEC-MTC).
• Drug Dosing: Aim to maintain drug levels within the therapeutic window.
• Enzyme Inhibitors: Reduce drug clearance, potentially increasing toxicity.
• Enzyme Inducers: Increase drug clearance, potentially reducing effectiveness.
• Pharmacokinetic Quantification: Crucial because it avoids guesswork about drug doses, leading to safe and effective treatments.
• Patient Data: Use patient data to adjust doses for better drug exposure.
• Dose-Exposure Relationship: Essential to optimize drug dosing for patients.

Methods for Establishing Dose-Exposure Relationship

• Statistical Methods: Analyze data to find mean residence time.
  • IV bolus is assumed to be 100% available from injection.
  • Oral is assumed to peak and then decline.
• Physiologically-Based Pharmacokinetic (PBPK) Models:
  • Divides the body into compartments, modeling drug flow.
  • Considers both intrinsic and extrinsic factors.
  • Separates drug factors and patient factors.
  • Requires extensive data.
• Compartmental Modeling Methods:
  • Focuses on the number of compartments needed to model drug distribution.
  • Considers input type (e.g., IV bolus), number and type of compartments (1, 2, or 3), dose type (single or multiple), and elimination type (linear or non-linear).

Compartment Models

• One-Compartment Model: Single compartment representing the whole body, with elimination.
• Two-Compartment Model: Drug first enters central compartment, moves to a peripheral one, then eliminates from central.
• Three-Compartment Model: One central, and two peripheral compartments (shallow and deep).

One-Compartment IV Bolus Model

• Assumptions: Single dose, single pathway (e.g., urinary excretion), immediate and even distribution, first-order elimination, and constant clearance.
• Elimination Rate Constant (ke): The rate at which the drug is eliminated.
• Amount of Drug at Time (t): X(t) = X(0) * e^(-ke*t)

Volume of Distribution (Vd)

• Definition: Relates drug in the body to drug in plasma.
• Not Necessarily Physiological: A factor relating total drug input to observed plasma levels.
• Plasma Concentration Calculation: Concentration = (C0) * e^(-ke*t), where C0 = Dose/Vd.

Concentration-Time Plot of IV Bolus

• Plot: Plasma concentration plotted against time.
• Shape: Initially high concentration, decreasing exponentially over time.
• Semi-log Plot: Easier to extract pharmacokinetic parameters from a straight line.
• Analysis: Allows extrapolating the elimination rate constant.

Modeling Data

• Data Used: Observed concentration-time points.
• Goal: Parameterize PK characteristics for clinical use.

Key Factors in Concentration-Time Profiles

• Initial Concentration (C0): Dose/Vd; higher dose or lower Vd leads to higher C0.
• Elimination: Rate the drug leaves the system; larger ke = faster elimination.
• Clearance Variations: Renal/hepatic function, drug-drug interactions, genetics.

Relationship Between Clearance, Volume of Distribution, and Elimination Rate Constant

• Clearance (CL): Drug cleared per unit of time (e.g., L/hr).
  • CL = ke * Vd
  • CL = rate of excretion/plasma concentrations
• Half-Life (t1/2): Time to eliminate half the drug.
  • t1/2 = 0.693/ke
  • t1/2 = 0.693 * Vd / CL

Clinical Data & Calculations

• Half-Life Calculation: Use two concentration points at different times.
• t1/2 = (ln(C1/C2) / ln(2)) * (t2-t1)
• Relationships: Changes in clearance do not affect volume of distribution vice versa.
• Clearance and Vd: The primary parameters.

Units of Measure

• Elimination Rate Constant (ke): Inverse time (1/hour or 1/minute).
• Clearance (CL): Volume per time (L/hr or mL/min).
• Volume of Distribution (Vd): Volume (L or mL).
• Half-Life (t1/2): Time (hours or minutes).