Therapeutic Drug Monitoring

The proper timing of blood sampling for the purposes of determining serum drug level, as well as the interpretation of the reported level require consideration of the pharmacokinetic properties of the drug being measured.  Some terms used in discussion of these properties are defined as follows:

Half-Life

The time required for the serum 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 serum concentration, and the time required to reach steady state.

Steady State

Steady state serum 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 serum concentration are the rate at which the drug is administered and the drug’s total clearance in that particular patient.

Peak Serum Concentration

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

Trough Serum Concentration

The minimum serum 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, 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.

Distribution

The dispersion of the systemically available drug from the intravascular space into extravascular fluids and tissues and thus to the target receptor sites.

Therapeutic Range

That range of serum 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 serum levels below the lower limit of the range, while others will require serum levels exceeding the upper limit for therapeutic benefit.

Correct timing of sample collection is important, since drug therapy is often revised on the basis of serum concentration determinations.  The absorption and distribution phases should be complete and a steady-state concentration achieved before the sample is drawn.  Levels obtained before a steady-state concentration exists may be erroneously low; increasing 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.

The timing of blood samples in relation to dosage is critical for correct interpretation of the serum concentration result.  The selection of the time that the sample is drawn in relation to drug administration should be based on the phamacokinetic 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 serum level monitoring of drugs with short half-lives, both a steady state peak and trough sample may be collected to characterize the serum concentration profile; for drugs with a long half-life, steady-state trough samples alone are generally sufficient.