PK 11: IV Infusions Flashcards
What are the advantages of IV fusions?
- precise control of drug delivery – increase/decrease rate of administration to achieve desired effect, stopped if experiencing toxicity
- maintenance of consistent concentrations – narrow therapeutic index drugs
What are the disadvantages of IV fusions?
- invasive (IV access)
- institutional settings
- inconvenient – external infusion pump, reduced vascular access available
What are narrow therapeutic index drugs?
- therapeutic concentrations are close to or overlap with those that elicit toxic responses
- continuous IV infusions allow for precise targeting of therapeutic concentration (minimal fluctuations)
One-Compartment IV Infusion Model
- R0: zero-order infusion rate (input)
What is steady-state?
drug accumulates in the body until steady-state is reached
- rate of input = rate of output
- rate of drug administration (R0) = rate of drug elimination (k x A)
- as time → ∞, Ct ≈ Css
What are the 2 parameters that influence concentration at steady-state (Css)?
- rate of infusion (R0)
- drug clearance (CL)
Understand the relationship between t1/2 and time required to achieve steady-state.
- time to steady-state is completely dependent on drug half-life
- clinically, we conclude steady-state is achieved after 4-5 half lives (97%)
- to calculate how long it will take to achieve steady-state concentrations after initiation of drug infusion, calculate t1/2 and multiply by 5 (or could use Ct equation)
What permits target concentrations to be achieved faster?
IV bolus + IV infusion combinations
OR
IV fusions with different rates
Post-Infusion
when the infusion is stopped, concentrations fall according to the first-order elimination rate constant – identical to those computed for a 1-compartment bolus model
- can calculate post-infusion concentrations using separate equations or combined equation
What is the principle of superposition?
early doses of drugs do not affect pharmacokinetics of subsequent doses (each dosing event is considered to be independent)
What is the implication of superposition?
concentrations following separately administered dosages can be computed as the sum of each independent dosing event
What is the applicability of superposition?
drugs following linear PK (first order processes and constant PK parameters)
Design an IV bolus + IV infusion-based dosing regimen.
- loading (IV bolus) dose is administered at the same time as initiation of the IV infusion (continuous) to rapidly achieve target drug concentrations
- for an appropriately computed loading dose + IV infusion combination, concentrations are immediately at target
Design a dosing regimen for IV infusions with different rates.
drugs where IV bolus dosing may be inappropriate
- elicit adverse reactions when administered rapidly IV
- serious dose-limiting toxicities (cannot withdraw a IV bolus dose)
for such drugs, use of rapid then slow infusion rates can be implemented to achieve target concentrations faster
- computing overall concentration after fast then slow IV fusion
What are primary PK parameters?
- independent of one another – ie. CL does not depend on V
- can be directly related to aspects of organism anatomy/physiology
