Drug Half-Life Studies
Jeffrey L. Segar, MD
Peer Review Status: Internally Peer Reviewed
Purpose: To Determine Patient Drug Kinetic Parameters Enabling Optimal Dosage Selection
When To Use:
Drug half-life studies are most valuable in cases of:
A. drug with narrow therapeutic index (little difference between therapeutic and toxic blood levels).
B. unpredictable variations in individual pharmacokinetics (i.e., aminoglycosides in neonates).
C. suspected alteration of drug metabolism and/or elimination (renal disease, liver disease, shock, etc.)
How To Accomplish Accurate T1/2 Determination:
In most situations, half-life studies should be done rather than single "peak" or "trough" studies - particularly in situations I.A - I.C above.
A. Blood sampling times should be selected to assure maximum accuracy. This means that one should avoid sampling "too close to the time of administration" (drug still being infused) yet not sample at a time when the concentration of drug may be too low to chemically detect.
B. The time interval between sampling should be sufficient to allow the drug concentration to decrease by one-half (i.e., T 1/2). This will avoid errors in "extrapolation". If the patient is known or suspected of having a prolonged T 1/2, the draw times should be greater in interval than the prolonged T 1/2, but not greater than the dosing interval (see recommendation in Table 2).
C. Two or preferably three blood samples should be drawn to assure greatest accuracy.
All information regarding patient's weight, drug dose, dosing interval, time of administration, route of administration, and time blood samples were drawn should be provided. This information will then appear in the chart record and will allow accurate pharmacokinetic calculations to be made.
|kel =||ln Co - ln Ct
|( Co: initial concentration; Ct: concentration after time = t)|
|t 1/2 =||0.693
|T= log (Cmax/Cmin) x 3.3 x t 1/2|
|(Cmax: maximum concentration after dose)|
|Cmin: trough concentration)|
When To Do T1/2 Studies Vs. Single Time Blood Level Studies
Single blood level determinations have only limited utility since they can be used for dosage adjustment only on a very limited scale. They are useful as a screening procedure to assure that adequate dosing is being accomplished. Drugs with relatively longer half-lives (very little difference in peak and trough levels) can ordinarily be followed by single blood levels determinations.
When a single blood level is used for monitoring the progress of the patient, be sure to select a time which avoids problems of IV delivery time. Generally, a -2-3 hour single time point- following IV administration is best.
|Digoxin||(1)||6-8 hrs. post dose|
|Phenobarbital||(2)||Time consistent with previous levels (if any)|
|Phenytoin||(2)||Depends on formulation|
|Theophylline||(3)||2 hrs. post dose (rapidly dissolving tablet or liquid)|
In general, T 1/2 studies are not absolutely needed until several doses of the drug have been given (1 to 2 days). The exception is the patient with severe organ dysfunction who will require repeated blood level determinations to adjust dosage. In these compromised patients, T 1/2 studies should be done after the first dose and before subsequent dosing. T 1/2 studies only need to be repeated if a marked change occurs in the patient's organ function status.
|Selected Dosing Interval (hr.)||Recommended T 1/2 Sampling Times (hr.)|
*Sampling within 1 hr. of drug administration is likely to be confusing because some drug may still be in the process of being infused or absorbed.
|Peak (ug/ml)||Through (ug/ml)|