CLINICAL PHARMACOKINETICS

Before using drugs for therapeutic intervention in individual patients, the

following decisions must be made.

1. the choice of drug must be made (e.g. drug, dosage form & route of administration)

2. an observable pharmacological effect or end point may be selected (e.g. lowering of fever, normalize heart rate)

3. rate of drug input manipulated until their end point is achieved (e.g. therapeutic drug monitoring)

• With an intended effect (as well as the known unintended toxic/side effects) after drug has been administered, one must increase or decrease drug input rate (e.g. size of dose & dosing frequency).
• The point here is that lack of observable effect for drugs could cause the adjustments in drug input rates to be implemented and without knowing whether such changes will benefit the patient.

For example, remember your 64 year-old patient with renal failure receiving Gentamycin treatment for sepsis. You don’t see him improving with your current dose (80mg OD) so you decide to increase it to 80mg BID but you know that the drug is also nephrotoxic and has a narrow therapeutic window. A little adjustment could produce more harm than treatment and you can’t determine this by just looking at your patient.

• A target concentration is needed to decide any change in drug input rate or when pharmacological endpoint cannot be monitored. 

• Therefore, an alternative approach is to define a TARGET CONCENTRATION (it should be within the therapeutic window as set by the MEC and MTC) of drug rather than an observable effect as the end point.

• The plasma concentration of the drug is usually selected because a patient's tissue samples cannot be obtained or the location of the specific site to be sampled may be uncertain.

When is there a need to define Target Concentration?

1. Pharmacological end point is not visible (e.g. small or large improvement of sepsis with antibiotic treatment, can you determine that?)

2. The TI is narrow. (near to 1, therapeutic window is narrow, for example MTC-MEC=0.00023)

3. When drug input needs to be manipulated due to changes in patient response

4. If it is not possible to visualize an organ

5. When it is not justified to take tissue samples or when it is difficult to extract tissue samples to monitor drug levels objectively (again, you already know this).


In providing instructions for the treatment of a patient, the following must be specified:

1. the dosing schedule (e.g. OD, BID, QID)

2. the choice of drug

3. mode and route of administration must be specified


Pharmacokinetic considerations have a major role in the following:

1. establishing the dosing schedule

2. adjusting an existing dosing schedule

3. to increase effectiveness of the drug

4. to reduce symptoms of toxicity

Remember your “AIM”