Bobbala_814_3_IV_Bolus_I_25

Page 1: Introduction

• Title: Intravenous Bolus Administration I

• Institution: West Virginia University, School of Pharmacy

• Instructor: Sharan Bobbala, Ph.D., Assistant Professor

Page 2: Objectives

• Explain Multiple Drug Dosing: Understand the concept of superimposition in drug dosing.

• Define Steady State: Relation between steady state and a drug’s half-life.

• Describe Accumulation Factor: Explore its role in multiple dosing.

• Calculate Peak Concentration: Learn to calculate peak concentration at steady state for IV bolus multiple dosing.

• Estimate Minimum Concentration: Evaluate trough concentration at steady state for IV bolus multiple dosing.

Page 3: Intravenous (IV) Bolus Injection

• Definition: IV bolus - complete drug injection at once into the bloodstream.

• Advantages: This method bypasses absorption processes, enabling direct entry into systemic circulation.

• Therapeutic Effects: Often a single dose is insufficient for desired therapeutic effect, leading to the necessity of multiple dosing.

• Example: Rapid IV boluses administered at constant intervals can be modeled using a one-compartment model with first-order elimination.

Page 4: Pharmacokinetics (PK) Dosing

• Multiple Doses: PK parameters vital for dosing such as elimination rate constant (k), volume distribution (V), and dosing interval (τ).

• Goal: Maintain therapeutic concentration within a prescribed range.

• Dosing Interval (τ): Defined as the time between successive doses.

Page 5: Plasma Drug Concentrations

• Graph Representation: Plasma concentrations after first and second doses; C0 represents Cmax (maximum concentration).

• Cmax in Multiple Dosing: Cmax indicates the highest drug concentration achieved post-dose.

Page 6: Cmax2 Calculation

• Superimposition: Early doses should not impact pharmacokinetics such as clearance of subsequent doses; graphs of drug concentration vs. time remain superimposable.

• Accumulation Impact: Later doses may yield higher concentrations due to drug accumulation.

Page 7: Graphical Superimposition

• Concentration Representation: Showcases Cmax values across different doses.

• Time Consideration: Illustrates gradual increase in Cmax with successive doses.

Page 8: Cmax2 Calculation Formula

• Cmin1 Definition: Concentration just before the arrival of the second dose.

• Cmax2 Relation: Cmax2 = Cmax1 + Cmin1 where Cmin1 = Cmax1e^(-kτ).

• Final Formula: Cmax2 = Cmax1(1 + e^(-kτ)).

Page 9: Cmax2 Simplification

• Equation Significance: This formula is essential to derive concentration after the next administered dose, using known parameters like Cmax1 and k.

Page 10: Understanding Dosing Interval

• Question: What does tau (τ) represent?

• Options: A) Peak dose B) Dosing interval C) Minimum dose.

Page 11: Cmax2 Calculation Example

• Data Input: Given Cmax1 = 200 mg/L, K = 0.60 hr–1, t = 6 hours.

• Options for Cmax2: A. 200 mg/L B. 5.4 mg/L C. 205.4 mg/L D. 223 mg/L.

Page 12: Reaching Steady State

• Steady State Definition: Achieved when drug elimination rate matches drug administration rate.

• Goal: Sustain the drug concentration within a therapeutic range.

Page 13: Drug Accumulation Mechanics

• Accumulation Explanation: After multiple doses, drug levels rise until elimination matches intake.

• Equilibrium: Drug in = drug out signifies reaching steady state.

Page 14: Time to Steady State

• Half-Life Relation: Steady state generally takes about five half-lives to achieve.

• Percentage Table: Each half-life results in increasing percentages towards steady state (e.g. 75% at 2 half-lives).

Page 15: Steady State by Half-Life

• Visual Aid: Chart demonstrating percentage of steady state over five half-lives.

Page 16: Impact of Half-Life on Steady State

• Observation: Shorter half-lives lead to quicker steady state achievement.

Page 17: Methods to Increase Steady State Concentrations

• Method 1: Increase drug dose while keeping the same dosing interval to widen concentration fluctuations.

• Method 2: Maintain dose but increase frequency to reduce peak-trough fluctuation.

Page 18: Accumulation Factor

• Definition: The concentration at any time after n doses; this may not necessarily reflect steady state conditions.

Page 19: Cmax and Dosing Intervals

• Cmax Equation: Formula showing relationship between maximum drug concentrations and dosing intervals.

Page 20: Accumulation Factor for Large Doses

• Condition: When n > 4 doses, accumulation factors become simplified for steady state estimations.

Page 21: Peak Concentration Calculation at Steady State

• Equation Use: For > 4-5 doses, achieving steady state allows for simplification of assessment equations.

Page 22: Trough Concentration Estimation

• Trough Definition: Concentration before the next bolus dose, calculable using specific equations.

Page 23: Average Steady-State Concentration

• Calculation Basis: Dependence on the initial dose (X0) and dosing interval (τ) for determining average concentrations at steady state.

Page 24: True/False Statement

• Statement: At steady state, the amount of drug eliminated during one dosing interval equals the drug dose.

• Answer: Test your understanding of the relationship.

Page 25: Peak Concentration Example

• Example Provided: Determine peak drug concentration for a 50 mg IV every 6 hours with given parameters.

• Options for Answers: A. 1.5 mg/L B. 4.4 mg/L C. 5.7 mg/L D. 35 mg/L.

Page 26: Trough Concentration Example

• Question: What is the trough concentration if IV bolus of 50 mg is given every 6 hours?

• Answer Options: A. 0.41 mg/L B. 0.7 mg/L C. 2 mg/L D. 5 mg/L.

Page 27: Average Concentration Evaluation

• Scenario: Assess average concentration during 1000-mg IV dosing every 8 hours at steady state.

• Options: A. 6.1 mg/L B. 10.5 mg/L C. 12.5 mg/L D. 22 mg/L.

Page 28: Summary

• Therapeutic Duration: Many clinical scenarios demand prolonged therapeutic effects beyond a single dose.

• Superimposition Results: If early doses don’t change pharmacokinetics, concentration-time curves for multiple doses appear the same.

• Steady State Timeframe: Faster elimination correlates with quicker steady state achievement. Rule of thumb: approximately five half-lives is required for 97% steady state.

• Accumulation Dynamics: Accumulation persists until the elimination equals the administration rate.

Page 29: Closing

• Contact Information: Sharan Bobbala, Ph.D. Email: sharan.bobbala@hsc.wvu.edu

• Acknowledgment: Thank you for your attention!