Loading dose
Calculate the dose needed to reach a target plasma concentration immediately, rather than waiting the five half-lives that maintenance dosing alone would require.
High-consequence calculationA loading dose delivers a large amount of drug at once and is a recognised source of serious dosing errors. Verify the volume of distribution, the target concentration, and the bioavailability independently before administration.
What is this for?
A loading dose fills the volume of distribution to the desired concentration in one step. It depends only on the volume of distribution and the target concentration, corrected for bioavailability — it does not depend on clearance, which is what distinguishes it from the maintenance dose.
How to use it
- Enter the target plasma concentration. Confirm it against a current reference — therapeutic ranges are revised.
- Enter the volume of distribution, choosing whether your source gives it in absolute litres or per kilogram. If per kilogram, add the weight.
- Enter the bioavailability as a fraction — 1 for intravenous.
Worked example
A drug has a volume of distribution of 0.7 L/kg. A 70 kg patient needs a plasma concentration of 20 mg/L. Calculate the intravenous loading dose.
Answer: Vd = 0.7 × 70 = 49 L. LD = (20 × 49) ÷ 1 = 980 mg.
Clinical pearls & pitfalls
- The loading dose does not depend on clearance. This is why it is unchanged in renal impairment even though the maintenance dose must be reduced — a point that is frequently missed.
- mg/L and mcg/mL are numerically identical. Therapeutic ranges are quoted in both, and mixing them up is not an error, but confusing either with mg/dL is.
- For drugs with a slow distribution phase, giving the whole loading dose as one rapid bolus produces a transient toxic peak before distribution completes. Digoxin is loaded in divided doses for exactly this reason.
- If a patient has already received some drug, subtract the amount already in the body — the loading dose is only the gap between the current and target concentrations.
Assumptions & limitations
- Assumes a one-compartment model with instantaneous distribution. For multi-compartment drugs the initial concentration after a bolus is far higher than the calculated steady-state value.
- Uses a population volume of distribution, which varies substantially between individuals and is altered by obesity, oedema, ascites, and critical illness.
- Does not account for drug already present. Recalculate against the measured concentration if the patient has had recent doses.
- Says nothing about infusion rate. Several loading doses must be given slowly to avoid rate-related toxicity — phenytoin and vancomycin are examples.
References
- Rowland M, Tozer TN. Clinical Pharmacokinetics and Pharmacodynamics. 4th ed. Lippincott Williams & Wilkins.
- Bauer LA. Applied Clinical Pharmacokinetics. 3rd ed. McGraw-Hill.
- Institute for Safe Medication Practices. ISMP List of High-Alert Medications in Acute Care Settings.