Final answer:
The clinical use of free drug level monitoring is crucial in drug discovery, TDM, and pharmacodynamic and pharmacokinetic studies; particularly when a drug has a narrow therapeutic range or significant inter-individual response variability. Free drug levels might not be as useful when the therapeutic index is broad, there is no clear correlation between concentration and effect, or reliable measurement methods are absent.
Step-by-step explanation:
When the clinical response does not agree with total drug concentration, free drug levels may be of clinical use in many cases. However, the instance where free drug levels would not be of significant use is not explicitly mentioned in the provided information. Generally, free drug concentration monitoring is beneficial in scenarios involving drug discovery, clinical therapeutic drug monitoring (TDM), and various clinical pharmacodynamic and pharmacokinetic studies. The monitoring is essential, particularly when drugs meet specific criteria such as a narrow therapeutic range, significant inter-individual variability, a clear relationship between blood exposure and clinical effect, and a validated bioanalytical method for measurement.
An understanding of pharmacokinetics, including aspects like drug half-life and plasma protein binding, is crucial in the development of new drug candidates as well as the management of drug therapies in individuals. Factors like drug half-life influence dosing intervals, while plasma protein binding informs on the portion of the drug that is available to exert therapeutic effects. Advanced techniques such as LC-MS/MS are frequently used to quantify unbound drug fractions and help in the process of dose optimization.
Cases where free drug levels may not be as useful:
When the drug has a wide therapeutic index and low variability in response among individuals.
If no direct correlation exists between plasma concentration (free or total) and drug effect.
When accurate and reliable bioanalytical methods for measuring free drug concentrations are lacking.