Maintenance Dose Calculator
Maintenance Dose Calculator
Calculate the maintenance dose per interval from clearance, target steady-state concentration and dosing interval — the dose that must fall in renal or hepatic impairment.
Maintenance Dose
CL × Css × intervalClearance 4.2 L/h, target 15 mg/L, interval 12 h, bioavailability 1 (intravenous)
Formula
- CL
- clearance in litres per hour, adjusted for the patient's renal or hepatic function
- Css
- target average steady-state concentration, in mg/L
- interval
- the dosing interval in hours — it sets the peak-to-trough swing, not the average concentration
- F
- bioavailability — 1 for an intravenous dose, the absorbed fraction for an oral one
Worked example
Clearance 4.2 L/h, target 15 mg/L, interval 12 h, bioavailability 1 (intravenous)
4.2 × 15 = 63 mg cleared per hour at steady state
63 × 12 = 756 mg per 12-hour interval
756 ÷ 1 = 756 mg per dose
How close to steady state, by half-lives elapsed
| Half-lives elapsed | Percentage of steady state reached |
|---|---|
| 1 | 50% |
| 2 | 75% |
| 3 | 88% |
| 4 | 94% |
| 5 | 97% |
Changing the dose and the interval together
| Change | Average concentration | Peak-to-trough swing |
|---|---|---|
| Halve the dose, halve the interval | Unchanged | Smaller |
| Double the dose, double the interval | Unchanged | Larger |
| Double the dose, same interval | Doubled | Larger |
Matching clearance, and waiting for steady state
The maintenance dose replaces what clearance removes. At steady state the rate in equals the rate out, so the dose per interval is clearance × target steady-state concentration × interval, divided by bioavailability for a non-intravenous route. It scales directly with clearance, which is why this — and not the loading dose — is the number that must fall in renal or hepatic impairment. Keep the units consistent: clearance in L/h multiplied by a concentration in mg/L gives milligrams per hour, and multiplying by an interval in hours gives milligrams per dose.
Steady state takes four to five half-lives, and that is true regardless of the dose given. A level drawn before then underestimates where the patient will finish, and a dose increased on the basis of an early level overshoots, because the concentration continues rising towards its own plateau on top of the increase. This is why the time a level was taken has to be recorded twice over — relative to the dose, and relative to the start of therapy. A concentration without that context cannot be interpreted at all.
The dosing interval determines the peak-to-trough swing rather than the average concentration. Halving both the dose and the interval leaves the average unchanged but makes the swings smaller; doubling both does the reverse. Whether that matters depends on the drug. For agents with concentration-dependent toxicity, or whose effect depends on time above a threshold — beta-lactams are the classic case — the interval is a real therapeutic lever. For drugs where the average concentration drives the effect, it makes little difference and convenience can decide.
Clearance here means population clearance adjusted for the individual patient: renal function for renally cleared drugs, hepatic function and liver blood flow for those cleared by the liver. It is the single largest source of error in the calculation. A creatinine-based estimate in a patient with low muscle mass, unstable renal function or an unrepresentative weight will be wrong, and the dose will be wrong in the same direction. Treat the result as a starting point to be confirmed by a properly timed level once steady state is reached, not as a final answer.
Frequently asked questions
How is a maintenance dose calculated?
Clearance in L/h × target steady-state concentration in mg/L × dosing interval in hours, divided by bioavailability. With a clearance of 4.2 L/h, a target of 15 mg/L and a 12-hour interval given intravenously, that is 756 mg per dose.
Why does the maintenance dose fall in renal impairment when the loading dose does not?
The maintenance dose matches clearance, so it falls when clearance falls. The loading dose fills the volume of distribution, in which clearance plays no part, so it is unchanged.
How long does it take to reach steady state?
Four to five half-lives, regardless of the dose given. A larger dose reaches a higher plateau but does not reach it any sooner, so a level drawn before then underestimates the eventual concentration.
Does changing the dosing interval change the average concentration?
No, provided the total daily dose is unchanged. Halving both the dose and the interval keeps the average the same but reduces the peak-to-trough swing, which matters for drugs with concentration-dependent toxicity or a time-above-threshold effect.
When should a level be taken to check the dose?
Once four to five half-lives have passed, and at a defined point in the dosing interval — usually the trough. The result must be reported with the time it was taken relative to the dose, because a level without a timing cannot be interpreted.
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References
- Winter ME. Basic Clinical Pharmacokinetics. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2010.
- Rowland M, Tozer TN. Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2011.
- Joint Formulary Committee. British National Formulary. London: BMJ Group and Pharmaceutical Press.