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Drug therapy in chronic disease situations requires systemic drug levels to reach target steady-state levels for maximum safety and efficacy. The time it takes for a drug to reach steady-state is a function of the elimination half-life of the drug. The following table illustrates how long it will take to achieve steady-state relative to the half-life:

# of half-lives % of Steady-State
1 50%
2 75%
3 87.5%
4 93.8%
5 96.9%

To achieve steady-state, you need approximately 5-7 half-lives of the drug. For drugs with rapid elimination and short half-life values, this is not a problem; however drugs with slow elimination could require days or weeks to achieve steady-state. If therapeutic effects are needed quickly, and the drug has a long half-life, one can use a loading dose to achieve therapeutic levels on the first dose. The loading dose rapidly achieves the therapeutic response and subsequent doses maintain the response.

The loading dose can be determined using the following equation:

$\textrm{Loading dose}=\frac{\textrm{Maintenance dose}}{(1-e^{-k\tau})}$

where τ is the dosing interval for the maintenance dose, and k is the terminal elimination rate constant.

Every patient is different. Thus, they react to drugs in different ways. Precision dosing is a key step toward achieving the goals of precision medicine, a global objective supported by world leaders. The emerging precision dosing field harnesses the explosion of genomic data and various markers of bodily functions using mathematical modeling to ensure that individuals get the best possible treatment.

Watch our webinar to learn how modeling and simulation approaches support the goal of precision dosing—providing the right drug dose to maximize therapeutic benefit, while reducing risk for each individual patient.

### 筆者について

By: Nathan Teuscher