Loading Dose Calculator
Loading Dose Calculator
Calculate a loading dose from volume of distribution, weight and target concentration — and see why it does not change in renal or hepatic impairment even though the maintenance dose does.
Loading Dose
Vd × weight × targetVd 0.7 L/kg, weight 70 kg, target 15 mg/L, bioavailability 1 (intravenous)
Formula
- Vd
- apparent volume of distribution — the volume that would hold the whole dose at the measured plasma concentration, not an anatomical volume
- target
- the plasma concentration the load is intended to achieve once distribution is complete, in mg/L
- F
- bioavailability — 1 for an intravenous dose, the absorbed fraction for an oral one
- clearance
- does not appear: a loading dose fills a volume and is independent of how fast the drug is removed
Worked example
Vd 0.7 L/kg, weight 70 kg, target 15 mg/L, bioavailability 1 (intravenous)
0.7 × 70 = 49 L total apparent volume of distribution
49 × 15 = 735 mg
735 ÷ 1 = 735 mg intravenously
Volume of distribution for common monitored drugs
| Drug | Vd (L/kg) | Where the drug sits |
|---|---|---|
| Gentamicin | 0.25 | Largely extracellular fluid |
| Theophylline | 0.5 | Total body water, roughly |
| Phenytoin | 0.7 | Total body water |
| Vancomycin | 0.7 | Total body water |
| Lithium | 0.7 – 0.9 | Total body water |
| Digoxin | About 7 | Mostly tissue — myocardium and skeletal muscle |
Loading dose versus maintenance dose
| Loading dose | Maintenance dose | |
|---|---|---|
| Determined by | Volume of distribution | Clearance |
| Changes in renal or hepatic impairment | No | Yes |
| Purpose | Reach the target concentration quickly | Replace what clearance removes |
Filling a volume, not matching a clearance
A loading dose fills the volume of distribution. It is volume of distribution × weight × target concentration, divided by bioavailability where the route is not intravenous, and it is independent of clearance. This is the point most often got wrong: because clearance does not appear in the equation, the loading dose does not change in renal or hepatic impairment even though the maintenance dose must. A patient with an eGFR of 15 needs the same digoxin or phenytoin load as a patient with normal renal function; it is only the doses that follow which are reduced.
Volume of distribution is an apparent volume, not an anatomical one. It is the volume that would be required to hold the whole dose at the measured plasma concentration, so for a drug that binds heavily to tissue it exceeds total body water by a wide margin — digoxin’s is around 7 L/kg, several times the volume of the body, because most of the drug is in myocardium and skeletal muscle rather than plasma. Drugs confined largely to extracellular fluid, gentamicin among them, have small values of around 0.25 L/kg.
Which weight to use follows from that. For drugs that do not distribute into fat — gentamicin and digoxin are the standard examples — use lean or adjusted body weight, or an obese patient will be substantially overloaded. For lipophilic drugs, actual body weight is closer to correct. Units have to be consistent: a volume of distribution in L/kg multiplied by a weight in kilograms gives litres, and multiplying that by a target in mg/L gives milligrams.
A loading dose given too fast causes toxicity even when the total amount is right, because the plasma concentration before distribution completes can be several times the eventual level. This is why intravenous phenytoin has a maximum infusion rate and why digoxin loading is divided into portions. The same distribution phase governs when a level can be taken: a concentration drawn before distribution is complete is high and uninterpretable, so a level means nothing unless the time it was drawn relative to the dose is recorded alongside it.
Frequently asked questions
How is a loading dose calculated?
Volume of distribution in L/kg × body weight in kg × target concentration in mg/L, divided by bioavailability. With a Vd of 0.7 L/kg, a weight of 70 kg and a target of 15 mg/L given intravenously, that is 735 mg.
Does the loading dose change in renal impairment?
No. Clearance does not appear in the loading-dose equation — the load fills a volume rather than matching a rate of removal. It is the maintenance dose that must be reduced in renal or hepatic impairment.
Why is digoxin's volume of distribution larger than the body?
Because it is an apparent volume, not an anatomical one. Digoxin binds heavily to myocardium and skeletal muscle, so very little remains in plasma, and the volume needed to hold the whole dose at that plasma concentration works out at around 7 L/kg.
Should I use actual or lean body weight?
Use lean or adjusted body weight for drugs that do not distribute into fat, such as gentamicin and digoxin, or an obese patient will be overloaded. Actual body weight is closer to correct for lipophilic drugs.
When can a level be taken after a loading dose?
Only after distribution is complete — six hours for digoxin, for example. A level drawn during the distribution phase is high and meaningless, and any level must be reported with the time it was taken relative to the dose.
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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.