Determination of Multiple Dosing Parameters: Loading and Maintenance Doses

A loading dose is an initial dose administered to rapidly achieve the target plasma drug concentration, ensuring a prompt therapeutic effect. It is particularly important for drugs with slow absorption or long half-lives.

For drugs exhibiting one-compartment pharmacokinetics, steady-state plasma levels can be achieved almost immediately with a single intravenous bolus and a short-term infusion.

Maintenance doses are administered after the loading dose to sustain plasma drug concentrations within the therapeutic range and prevent fluctuations below the minimum effective concentration.

The dose ratio defines the relationship between the loading and maintenance doses, ensuring that the proper therapeutic levels are maintained.

For drugs with rapid absorption and distribution, the loading dose can be calculated using the given equation.

Clinically, the loading dose can be approximated using a simplified formula, where represents the desired plasma drug concentration, S is the salt form of the drug, and F is the fraction of the drug that is bioavailable. However, this calculation is unsuitable for drugs showing multicompartment kinetics due to their slower extravascular distribution and delayed equilibration.