Drug Accumulation During Multiple Dosing: Intermittent IV Infusions

Intermittent IV infusion delivers drugs in short infusions followed by elimination periods, creating peaks and troughs that avoid prolonged high concentrations. Continuous infusion maintains steady drug levels throughout. Intermittent dosing reduces adverse effects and is often better tolerated than rapid IV bolus administration, making it ideal for drugs requiring specific concentration targets.

Aminoglycosides require high peak plasma concentrations for antimicrobial efficacy while maintaining low trough levels to prevent nephrotoxicity and ototoxicity. Intermittent IV infusion achieves this balance more effectively than bolus or continuous methods. This dosing strategy optimizes therapeutic outcomes while minimizing toxicity risks associated with sustained high drug exposure.

Steady-state concentrations may not be achieved during a single dosing cycle with intermittent infusion. However, repeated administration over multiple cycles allows drug accumulation to reach determination of multiple dosing parameters steady state minimum and maximum concentrations. This progressive accumulation ensures therapeutic levels are maintained across successive dosing intervals.

The continuous IV infusion equation is modified for intermittent infusion, where R represents infusion rate, D denotes dose size, and tinf is the infusion period. After infusion ends, first-order elimination equations calculate post-infusion concentration using Cstop (concentration when infusion stops) and elapsed time. These equations predict concentration changes throughout the dosing cycle.

Intermittent infusion delivers medications gradually rather than as rapid boluses, minimizing toxicity and side effects. This approach prevents sustained high drug concentrations that cause adverse reactions. By spacing doses with elimination periods, intermittent infusion provides a flexible strategy that optimizes therapeutic outcomes while reducing toxicity risks for drugs with narrow safety margins.

Peaks and troughs created by intermittent infusion prevent prolonged high concentrations that increase adverse effects. Low trough levels reduce cumulative toxicity, while controlled peaks maintain efficacy. This concentration pattern is particularly beneficial for drugs like aminoglycosides, where balancing high peak concentrations for efficacy against low troughs for safety is critical to successful therapy.

With repeated intermittent dosing, drug accumulation occurs when elimination between doses is incomplete. Each successive dose adds to residual drug from previous doses, gradually increasing peak and trough concentrations. This cumulative effect eventually leads to steady-state levels where drug input equals elimination, establishing consistent concentration patterns across dosing cycles.