In pharmacokinetics, a loading dose is an initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose.[1]

A loading dose is most useful for drugs that are eliminated from the body relatively slowly, i.e. have a long systemic half-life. Such drugs need only a low maintenance dose in order to keep the amount of the drug in the body at the appropriate therapeutic level, but this also means that, without an initial higher dose, it would take a long time for the amount of the drug in the body to reach that level.

Drugs which may be started with an initial loading dose include digoxin, teicoplanin, voriconazole, procainamide and fulvestrant.

One or series of doses that may be given at the onset of therapy with the aim of achieving the target concentration rapidly.

Worked example[edit]

For an example, one might consider the hypothetical drug foosporin. Suppose it has a long lifetime in the body, and only ten percent of it is cleared from the blood each day by the liver and kidneys. Suppose also that the drug works best when the total amount in the body is exactly one gram. So, the maintenance dose of foosporin is 100 milligrams (100 mg) per day—just enough to offset the amount cleared.

Suppose a patient just started taking 100 mg of foosporin every day.

  • On the first day, they'd have 100 mg in their system; their body would clear 10 mg, leaving 90 mg.
  • On the second day, the patient would have 190 mg in total; their body would clear 19 mg, leaving 171 mg.
  • On the third day, they'd be up to 271 mg total; their body would clear 27 mg, leaving 244 mg.

As one can see, it would take many days for the total amount of drug within the body to come close to 1 gram (1000 mg) and achieve its full therapeutic effect.

For a drug such as this, a doctor might prescribe a loading dose of one gram to be taken on the first day. That immediately gets the drug's concentration in the body up to the therapeutically-useful level.

  • First day: 1000 mg; the body clears 100 mg, leaving 900 mg.
  • On the second day, the patient takes 100 mg, bringing the level back to 1000 mg; the body clears 100 mg overnight, still leaving 900 mg, and so forth.

Calculating the loading dose[edit]

Four variables are used to calculate the loading dose:

Cp = desired peak concentration of drug
Vd = volume of distribution of drug in body
F = bioavailability
S = fraction of drug salt form which is active drug

The required loading dose may then be calculated as

For an intravenously administered drug, the bioavailability F will equal 1, since the drug is directly introduced to the bloodstream. If the patient requires an oral dose, bioavailability will be less than 1 (depending upon absorption, first pass metabolism etc.), requiring a larger loading dose.

Sample values and equations[edit]

Pharmacokinetic metrics
Characteristic Description Symbol Unit Formula Worked example
Dose Amount of drug administered. Design parameter 500 mmol
Dosing interval Time between drug dose administrations. Design parameter 24 h
Cmax The peak plasma concentration of a drug after administration. Direct measurement 60.9 mmol/L
tmax Time to reach Cmax. Direct measurement 3.9 h
Cmin The lowest (trough) concentration that a drug reaches before the next dose is administered. Direct measurement 27.7 mmol/L
Volume of distribution The apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration in plasma to drug amount in the body). 6.0 L
Concentration Amount of drug in a given volume of plasma. 83.3 mmol/L
Absorption half-life The time required for the concentration of the drug to double its original value for oral and other extravascular routes.[citation needed] 1.0 h
Absorption rate constant The rate at which a drug enters into the body for oral and other extravascular routes. 0.693 −1
Elimination half-‍life The time required for the concentration of the drug to reach half of its original value. 12 h
Elimination rate constant The rate at which a drug is removed from the body. 0.0578 h−1
Infusion rate Rate of infusion required to balance elimination. 50 mmol/h
Area under the curve The integral of the concentration-time curve (after a single dose or in steady state). 1,320 mmol/L·h
Clearance The volume of plasma cleared of the drug per unit time. 0.38 L/h
Bioavailability The systemically available fraction of a drug. Unitless 0.8
Fluctuation Peak trough fluctuation within one dosing interval at steady state.