Pharmacokinetics

Maintenance Dose Calculator

Calculates the dose per interval that keeps a drug at its target steady-state concentration, from clearance, bioavailability and the dosing interval.

Maintenance dose per interval

600.0mg every 12 h

1200.0 mg/day total · Twice daily

Inputs

Target steady-state concentration (Cₛₛ)

mg/L

Average level at steady state. Typical: digoxin 0.8–2.0 mcg/L, vancomycin 10–20 mg/L (trough), phenytoin 10–20 mg/L.

Clearance (Cl)

L/h

Volume of plasma cleared of drug per hour.

Bioavailability (F)

100% for IV. Leave blank for no adjustment.

Dosing interval (τ)

q12h = every 12 hours. Frequency: Twice daily.

Try an example drug

Working

MD = (Cₛₛ × Cl × τ) ÷ F10 × 5 × 12 ÷ 1

Dose per interval600.0mg

Total daily dose1200.0mg/day

FrequencyTwice daily

Steady state

Half-life estimated as 0.693 ÷ (Cl ÷ 50 L) — a typical Vd, not this patient's.

Estimated half-life6.9h

Time to steady state (4.32 × t½)29.9h (~2 days)

MD = (Cₛₛ × Cl × τ) ÷ F

t½ (estimate) = 0.693 ÷ (Cl ÷ 50 L); time to steady state = 4.32 × t½

R = 1 ÷ (1 − e^(−k × τ)); peak/trough = e^(k × τ); k = 0.693 ÷ t½

Cₛₛ = target steady-state concentration (mg/L); Cl = clearance (L/h); τ = dosing interval (h); F = bioavailability as a fraction. mg/L × L/h × h gives mg.

Steady state — rate in equals rate out; it is reached after 4–5 half-lives, independent of any loading dose, and the maintenance dose replaces the drug eliminated each interval.

Accumulation depends on the dosing interval relative to the half-life: a shorter interval means more accumulation, which matters for predicting toxicity.

Clinical application — start with the estimated dose, measure concentrations at steady state, adjust on therapeutic response, and allow for individual variability.

Worked example: Oral maintenance dose for a target average level

A teaching exercise: Drug X is to be given by mouth every 12 hours to hold an average steady-state plasma concentration of 12 mg/L. In this (illustrative) patient its clearance is 3 L/h, its oral bioavailability is 80 % and its half-life is 8 h. Find the dose per interval, the daily dose, and how the level will behave at steady state.

Target Cₛₛ (average): 12 mg/L
Clearance (Cl): 3 L/h
Bioavailability (F): 80 % (enter 80)
Dosing interval (τ): q12h = 12 h
Half-life (Enter half-life mode): 8 h

Maintenance dose
MD = (Cₛₛ × Cl × τ) ÷ F = (12 mg/L × 3 L/h × 12 h) ÷ 0.80 = 432 ÷ 0.80 = 540.0 mg
Check the units
mg/L × L/h × h = mg
Daily dose
540.0 mg × (24 h ÷ 12 h) = 1080.0 mg/day
Rate constant
k = 0.693 ÷ t½ = 0.693 ÷ 8 h = 0.0866 h⁻¹; k × τ = 0.0866 × 12 = 1.04
Time to steady state (~95 %)
4.32 × t½ = 4.32 × 8 h = 34.6 h (about 2 days)
Accumulation ratio
R = 1 ÷ (1 − e^(−1.04)) = 1 ÷ (1 − 0.354) = 1.55
Peak/trough ratio
e^(k × τ) = e^(1.04) = 2.83

MD = 540.0 mg every 12 h (1080.0 mg/day); steady state in ≈ 34.6 h; R = 1.55; peak/trough ≈ 2.83.

540 mg every 12 hours puts in, on average, exactly what 3 L/h of clearance removes when the mean level is 12 mg/L: 540 × 0.80 ÷ (3 × 12) = 12 mg/L. That 12 mg/L is the time-averaged level, not the peak or the trough. With a 12 h interval and an 8 h half-life the peak is about 2.8 times the trough, and steady-state levels are about 1.55 times those after the first dose. This is a teaching calculation on illustrative values: a real regimen is set by the prescriber from the drug's licensed dosing and the institution's protocol, rounded to an available strength, and confirmed by monitoring — not by this calculator.

Common mistakes

Typing F as a fraction into a percentage field. This page expects 80 for 80 %; entering 0.8 is read as 0.8 % and makes the dose 100 times too large.

Mismatching time units. Cl in L/h needs τ in hours; a clearance in mL/min must be converted first (mL/min × 60 ÷ 1000 = L/h), or the dose is out by a factor of 16.7.

Treating a trough or peak target as Cₛₛ. The formula gives the dose for the average steady-state level; a trough target (as for vancomycin) or a peak target (as for aminoglycosides) needs the intermittent-infusion equations instead.

Forgetting the salt factor. The formula gives mg of active drug; if the product is a salt (for example a hydrochloride or sodium salt), divide by the salt fraction S to get the mg of salt to give.

Expecting a bigger dose to reach steady state sooner. The time to steady state depends only on the half-life (about 4–5 half-lives); only a loading dose gets the level to target sooner.

Using Vd to work out the maintenance dose. Vd sets the loading dose and, with Cl, the half-life; the maintenance dose depends on clearance alone.

Assumptions and limitations

Assumes linear, first-order elimination: clearance is the same at every concentration. Drugs with saturable metabolism, such as phenytoin, do not follow this formula.

Assumes a one-compartment model and that clearance and F stay constant between doses; renal or hepatic change, interactions or illness alter both.

Cₛₛ is the average concentration over an interval. The accumulation and peak/trough figures treat each dose as an instantaneous (bolus-like) input and ignore absorption time.

Without an entered half-life, the page estimates t½ from Cl and an assumed Vd of 50 L for every drug, so the time to steady state shown in that mode is only a rough placeholder.

Does not round to available tablet or vial strengths and does not include a salt factor.

Guide: Pharmacokinetic Parameters: AUC, Clearance, Half-Life and BioavailabilityThe concept in full, with practice questions.Accumulation Index CalculatorExplore how R = 1 ÷ (1 − e^(−kτ)) changes as you shorten or lengthen τ for the same half-life.Elimination Rate Constant (kₑ) CalculatorTurn this patient's Cl and Vd into kₑ and t½, so you can enter a real half-life instead of relying on the 50 L estimate.Volume of Distribution CalculatorFind Vd, which with Cl gives the half-life and decides any loading dose.

References

Ducharme MP, Shargel L, editors. Shargel and Yu's Applied Biopharmaceutics & Pharmacokinetics. 8th ed. New York: McGraw Hill; 2022.
Rowland and Tozer's Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications. 5th ed. Philadelphia: Wolters Kluwer; 2019.

Common questions

At steady state the dose given each interval must equal the amount eliminated in that interval, and elimination is set by clearance. Vd decides the loading dose and how long steady state takes, not the maintenance dose.

No. Doubling τ doubles the dose per interval, so the total daily dose stays the same. What changes is the swing between peak and trough.

Without a half-life the calculator assumes a typical Vd of 50 L to turn clearance into a half-life. For drugs with a very large or small Vd (digoxin, aminoglycosides) enter the real half-life instead.

mg/L with clearance in L/h gives a dose in mg. A target in mcg/L (such as digoxin) gives the dose in mcg.

It gets the concentration to target immediately, but the time for the maintenance regimen itself to settle at steady state is still 4–5 half-lives.

Prepared by the PharmaWallah student team. Verify results with your textbook or instructor. Report an error · Editorial policy