Subscribe  |   Careers  |   Appointments

Therapeutic Drug Monitoring

Patients receiving treatment with drugs that have a narrow therapeutic index must be monitored for the blood level of the drug on a regular basis, as they are susceptible to toxic or under dosing. Generally, most samples are collected after the drug achieves a steady state concentration (usually after 5 X half-life of the drug). Blood concentrations obtained before a steady state is achieved may be erroneously low and any increase in the dosage based on such a result could produce toxic concentrations.

In addition, when making comparative measurements, it is important that the sampling time be consistent because the timing of blood sampling in relation to dosage is critical for the correct interpretation of the blood concentration result. Selection of the time at which the sample is drawn needs to take into account the time of drug administration, the pharmacokinetic properties of the drug, its dosage form and the clinical reason for assaying the sample (e.g. assessment of efficacy or clarification of possible drug-induced toxicity). For routine blood level monitoring of the steady state of drugs with short half-lives, both a peak blood concentration and trough blood concentration sample may be collected to characterize the blood concentration profile; for drugs with a long half-life, steady state trough samples alone are generally sufficient. There are exceptions such as for Digoxin which is usually collected 8 hours after the last dose.

In Pharmacokinetics (what the body does to the drug), the following definitions are used:

Half-Life

The time required for the blood concentration present at the beginning of an interval to decrease by 50%. Knowing an approximate half-life is essential to the clinician since it determines the optimal dosing schedule with oral agents, the intradose fluctuation of the blood concentration, and the time required to reach steady state.

Steady State

Steady state blood concentrations are those values that recur with each dose and represent a state of equilibrium between the amount of drug administered and the amount being eliminated in a given time interval.  During long term dosage with any drug, the two major determinants of its mean steady state blood concentration are the rate at which the drug is administered and the drug’s total clearance in that particular patient.

Peak Blood Concentration

The point of maximum concentration on the blood concentration-versus-time curve. The exact time of the peak blood concentration is difficult to predict since it represents complex relationships between input and output rates.

Trough Blood Concentration

The minimum blood concentration found during a dosing interval. Trough concentrations are theoretically present in the period immediately preceding administration of the next dose.

Absorption

The process by which a drug enters the body. Intravascularly administered drugs are absorbed totally (100% bioavailable), but extravascular administration yields varying degrees and rates of absorption. The relationship between the rate of absorption and the rate of elimination is the principle determinant of the drug concentration in the bloodstream. Also, it is important to note that the type of vehicle (excipient) that covers the active ingredient has significant impact on the absorption rate of a drug.

Distribution

The dispersion of the systemically available drug from the intravascular space into extravascular fluids and tissues and thus to the target receptor sites. This is significantly affected by the solubility of the drug (lipophilic vs. hydrophilic).

Therapeutic Range

That range of blood drug concentrations associated with a high degree of efficacy and a low risk of dose-related toxicity.  The therapeutic range is a statistical concept: it is the concentration range associated with therapeutic response in the majority of patients.  Consequently, some patients will exhibit such a response at blood levels below the lower limit of the range, while others will require blood levels exceeding the upper limit for therapeutic benefit.