Loading dose
Encyclopedia
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.
A loading dose is most useful for drugs that are eliminated from the body relatively slowly. Such drugs need only a low maintenance dose in order to keep the amount of the drug in the body at the appropriate 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
and procainamide
. Phenytoin
for acute status epilepticus
should also be given with an initial loading dose, co-administered with a benzodiazepine
, to immediately stabilize neuronal membranes and electrical activity during a seizure.
, 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.
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.
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.
A loading dose is most useful for drugs that are eliminated from the body relatively slowly. Such drugs need only a low maintenance dose in order to keep the amount of the drug in the body at the appropriate 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
Digoxin
Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...
, teicoplanin
Teicoplanin
Teicoplanin is an antibiotic used in the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. It is a glycopeptide antibiotic extracted from Actinoplanes teichomyceticus, with a similar...
, voriconazole
Voriconazole
Voriconazole is a triazole antifungal medication that is generally used to treat serious, invasive fungal infections. These are generally seen in patients who are immunocompromised, and include invasive candidiasis, invasive aspergillosis, and certain emerging fungal infections.-Invasive...
and procainamide
Procainamide
Procainamide INN is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias, classified by the Vaughan Williams classification system as class Ia.-History:...
. Phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
for acute status epilepticus
Status epilepticus
Status epilepticus is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 5 minutes, or recurrent seizures without regaining consciousness between seizures...
should also be given with an initial loading dose, co-administered with a benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
, to immediately stabilize neuronal membranes and electrical activity during a seizure.
Worked example
For an example, one might consider the hypothetical drug foosporin. Suppose it has a long lifetime in the bodyBiological half-life
The biological half-life or elimination half-life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH definition...
, 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
Four variables are used to calculate the loading dose:| Cp | = desired peak concentration Concentration In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration... of drug |
| Vd | = volume of distribution Volume of distribution The volume of distribution , also known as apparent volume of distribution, is a pharmacological term used to quantify the distribution of a medication between plasma and the rest of the body after oral or parenteral dosing... of drug in body |
| F | = bioavailability Bioavailability In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered... |
| S | = salt fraction |
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.