Learning Objective:
Calculate loading and maintenance doses for medications, understand the impact of bioavailability, volume of distribution, clearance, and half-life, and recognize when dose adjustments are needed in renal or hepatic impairment.
Proper dosage calculations ensure therapeutic drug levels are achieved safely and effectively. Two key types of doses are commonly used: loading dose and maintenance dose.
Loading Dose (LD)
- Purpose: Rapidly achieve the target plasma concentration (Cp).
- Formula:
| Symbol | Meaning |
|---|---|
| Cp | Target plasma concentration |
| Vd | Volume of distribution |
| F | Bioavailability (fraction of drug absorbed) |
Notes:
- The loading dose is usually unchanged in renal or liver disease.
- Used when an immediate drug effect is required (e.g., digoxin, phenytoin).
Maintenance Dose (MD)
- Purpose: Maintain steady-state plasma concentration over time.
- Formula:
| Symbol | Meaning |
|---|---|
| Cp | Target plasma concentration |
| CL | Clearance (volume/time) |
| τ | Dosing interval (time between doses) |
| F | Bioavailability |
Notes:
- Time to steady state depends primarily on half-life (t½), not on dose or dosing frequency.
- In renal or hepatic impairment, the maintenance dose often needs adjustment, while the loading dose usually remains unchanged.
- τ does not apply to continuous infusions.
Key Points for Clinical Practice
| Concept | Key Point |
|---|---|
| Loading dose | Rapidly achieves target Cp; depends on Vd, not clearance |
| Maintenance dose | Maintains steady-state Cp; depends on CL and dosing interval |
| Time to steady state | Determined by t½; independent of dose or frequency |
| Renal/liver disease | MD often reduced; LD usually unchanged |
