Final answer:
The main reason for suboptimal drug levels in therapeutic drug monitoring is the individual patient variability affecting drug ADME processes and nonadherence to treatment protocols, which are addressed through precise pharmacokinetic principles and sophisticated bioanalytical methods like LC-MS/MS.
Step-by-step explanation:
The main reason for suboptimal drug levels in therapeutic drug monitoring (TDM) is attributed to individual patient differences, including age, weight, genetic polymorphism, co-morbid diseases, and drug-drug interactions (DDI). These variables can affect the absorption, distribution, metabolism, and excretion (ADME) processes of drugs, causing substantial inter-individual variability in drug exposure for a given dose. Additionally, patient nonadherence to prescribed treatment regimens can further result in suboptimal drug levels, potentially leading to drug resistance, such as in the treatment of tuberculosis (TB).
To ensure optimal therapeutic drug levels, it is crucial to employ precise pharmacokinetic principles and bioanalytical methods like liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of drug concentration in plasma or serum. These techniques help in determining effective drug dosages by accounting for factors such as plasma protein binding, which influences the free, pharmacologically active fraction of the drug. Early drug discovery efforts aim to pre-emptively identify drug candidates with favorable pharmacokinetic properties to prevent suboptimal drug levels in later stages.