Kinetics of Multiple Dosing explains drug accumulation, steady state concentration, and dosing intervals in pharmacokinetics.
Kinetics of Multiple Dosing
When drugs are given at regular intervals (e.g., every 8 hours), the drug accumulates in the body until a steady state is reached.
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Key Concepts:
- Accumulation: Occurs when drug is administered before previous doses are fully eliminated.
- Peak and trough levels: Highest and lowest concentrations within a dosing interval.
Factors Affecting Multiple Dose Kinetics:
- Dosing interval (τ)
- Elimination half-life (t½)
- Dose (D)
- Volume of distribution (Vd)
- Clearance (Cl)
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Key Equations:
- Peak and trough concentrations after multiple doses:
- $C_{\text{max,ss}} = \frac{C_{\text{max,1}}}{1 – e^{-k \tau}}$
- $C_{\text{min,ss}} = C_{\text{max,ss}} \cdot e^{-k \tau}$
- Where:
- C₀: Initial concentration after a single dose
- k: Elimination rate constant
- t: Dosing interval
Clinical Significance:
- Prevents toxicity (due to accumulation) or sub-therapeutic levels.
- Determines appropriate dose frequency for chronic treatments (e.g., antibiotics, antiepileptics).
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