XXI 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.

This page was last modified: 12 February 2001

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