From the Guidelines
The loading dose for a medication is a crucial concept in clinical practice, and it is typically calculated based on factors such as the patient's weight, kidney function, desired blood concentration, and the volume of distribution of the drug in the body, with specific loading doses varying by medication, such as 20 mg/kg for phenytoin, as seen in 1. When considering the administration of a loading dose, it is essential to take into account the medication's pharmacokinetics and pharmacodynamics, as well as the patient's individual characteristics, such as age, weight, and renal function.
- The loading dose is usually higher than the maintenance dose, and it is given to rapidly achieve therapeutic blood levels, which is critical in urgent clinical situations where immediate therapeutic effects are needed.
- The specific loading dose varies by medication, and some common examples include:
- Phenytoin: 20 mg/kg, as seen in 1
- Fosphenytoin: 18 PE/kg, as seen in 1
- Levetiracetam: 1,500 mg, as seen in 1
- It is also important to note that the route of administration can affect the loading dose, with some medications being available in both oral and intravenous formulations, such as phenytoin and fosphenytoin, as seen in 1.
- In addition, the loading dose should be calculated carefully to avoid adverse effects, such as toxicity or hypotension, which can occur with certain medications, such as phenytoin, as seen in 1.
- Overall, the loading dose is a critical concept in clinical practice, and it requires careful consideration of the medication's pharmacokinetics and pharmacodynamics, as well as the patient's individual characteristics, to ensure safe and effective treatment, as supported by the evidence in 1 and 1.
From the FDA Drug Label
Some authorities have advocated use of an oral loading dose of phenytoin in adults who require rapid steady-state serum levels and where intravenous administration is not desirable Initially, one gram of Dilantin (extended phenytoin sodium capsules, USP) is divided into three doses (400 mg, 300 mg, 300 mg) and administered at two-hour intervals The loading dose of phenytoin is one gram, divided into three doses of 400 mg, 300 mg, and 300 mg, administered at two-hour intervals 2.
From the Research
Definition of Loading Dose
- A loading dose is given to rapidly achieve a desired drug concentration in the blood 3
- It is calculated based on the volume of distribution (Vd) at steady state, but using the central compartment Vd (Vc) or the Vd at steady state can result in high peak concentrations and possibly serious adverse effects
Calculation of Loading Dose
- The loading dose should be calculated from the Vd at the time of peak effect (tmax) to accurately achieve the target concentration without unexpected adverse effects 3
- If the loading dose is calculated from a Vd determined after the tmax, the actual concentration will exceed the target concentration at the tmax
- If a loading dose is calculated from a Vd before the peak effect occurs, the actual concentration will be insufficient to achieve the target concentration at tmax
Therapeutic Drug Monitoring
- Therapeutic drug monitoring (TDM) is a useful tool for the optimization of drug therapy, and can be used to evaluate the appropriateness of drug usage 4
- TDM can help identify patients with sub-therapeutic or above-therapeutic drug levels, and guide adjustments to the loading dose or maintenance infusion
Drug Interactions
- Pharmacokinetic interactions between drugs can be studied using single-dose or multiple-dose experimental designs 5
- Multiple dosing trial designs appear to be advantageous for investigating possible pharmacokinetic interactions, as they can detect interactions that may not be observed after single dosing