Maintenance Dose Formula
Maintenance dose = Cl × Css × τ / F.
Calculate the regular dose that maintains a steady-state drug concentration.
Essential clinical pharmacokinetics.
The Formula
The maintenance dose (MD) is the regular dose given at each dosing interval to maintain drug concentration at steady state. At steady state, the amount of drug eliminated between doses exactly equals the dose administered.
Cl is drug clearance (volume cleared per unit time, L/h), Css is the desired steady-state plasma concentration, τ (tau) is the dosing interval (hours), and F is bioavailability.
Drug clearance Cl = Vd × k_e = (0.693 × Vd) / t½. It represents how efficiently the body removes the drug. High clearance = drug eliminated quickly = need frequent or large doses. Renal or hepatic disease reduces clearance, requiring dose reductions.
The average steady-state concentration with a given dosing regimen: Css_avg = (F × MD) / (Cl × τ). This rearranges to give the maintenance dose formula above.
Steady state is reached after 4–5 half-lives regardless of dose size. A loading dose gets concentration into the therapeutic range quickly, while the maintenance dose keeps it there.
Example clearances: Gentamicin Cl ≈ 0.06 L/h/kg (renally eliminated). Theophylline Cl ≈ 0.04 L/h/kg (hepatically metabolized). Lithium Cl ≈ 0.02 L/h/kg (requires careful dosing due to narrow therapeutic window).
Variables
| Symbol | Meaning | Unit |
|---|---|---|
| MD | Maintenance dose | mg |
| Cl | Drug clearance | L/h |
| Css | Target steady-state concentration | mg/L |
| τ | Dosing interval | hours |
| F | Bioavailability (0–1) | Dimensionless |
Example 1
Drug with Cl = 5 L/h, target Css = 10 mg/L, dosed every 8 hours (τ=8), oral (F=0.8).
MD = (5 × 10 × 8) / 0.8 = 400 / 0.8
MD = 500 mg every 8 hours
Example 2
Same drug in a patient with 50% reduced clearance (Cl = 2.5 L/h due to liver disease).
MD = (2.5 × 10 × 8) / 0.8 = 200 / 0.8
MD = 250 mg every 8 hours (half the normal dose)
When to Use It
- Designing dosing regimens for chronic drug therapy
- Adjusting doses for organ dysfunction (renal/hepatic failure)
- Therapeutic drug monitoring (TDM) for narrow therapeutic index drugs
- Clinical pharmacokinetics training and pharmacy board exams