Clinical Applications of Pharmacokinetics
Objectives:
=> To understand the basics of a Therapeutic Drug Monitoring service
=> To understand the principles of the analytical methods, HPLC, GLC,
RIA, and EMIT
=> To describe and understand how changes in physiology effect the
pharmacokinetics of drugs in the very young and the elderly
We can start this topic by talking about the Clinical Pharmacy service,
Therapeutic Drug Monitoring. This involves the measurement and interpretation of
plasma/serum/blood concentrations in patients.
Therapeutic Drug Monitoring
Why
Therapeutic drug monitoring (TDM) becomes important when:
a) the drug has a narrow therapeutic-toxic range,
b) there is a large variability in pharmacokinetic parameter values between
patients,
c) the therapeutic effect is not readily assessed (e.g. antibiotics) or
clinical symptoms are to be avoided (e.g. seizure). Not as useful for blood
pressure lowering (can measure B.P. directly) or anticoagulants (again measure
clotting time directly),
d) there is a direct relationship between Cp or concentration in other
biological sample (e.g. saliva) and pharmacological effect,
e) an appropriate (accurate, short turn around, inexpensive) analytical
method is available for the drug,
f) the expected or desired therapeutic effect is not observed (may be
absorption or compliance problem),
g) a drug with high first pass effect is involved, or
h) a patients has altered and/or variable renal state and the drug is
eliminated mostly as unchanged drug in urine (fe less than 1)
Typical drugs
Table XXI-1 Therapeutic Concentration Ranges
| Drug |
Therapeutic Concentration Range |
| Aminoglycoside (gentamicin, tobramycin) |
0.5 <-> 8 mg/L |
| Digoxin |
0.5 <-> 8 2.0 ug/L |
| Phenytoin |
10 <-> 8 20 mg/L |
| Theophylline |
10 <-> 8 20 mg/L |
Procedure
Pharmacist and physician develop initial dosing recommendations
Information required
- Patient - Age, weight, sex, height, smoker
- Clinical - Drug requirements, clinical status (renal - serum creatinine;
cardiac - cardiac output, liver, etc.)
Calculate initial loading dose or maintenance regimen and make recommendations
Organize sample collection and analysis
Accurate Timing in necessary
Figure XXI-1. Illustrating the Effect of Sample Times on Parameter Values
Evaluate pharmacokinetically the analytical result and recalculate dosing
regimen recommendations
Organize further samples if necessary, repeat as necessary
Calculations
Computer or calculator programs can be used to help the bedside development of
dosing regimen. Other more sophisticated programs are available to calculate
values for the drug pharmacokinetics and make further recommendations.
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