Therapeutic drug monitoring reviewed
Xchange newsletter - Spring 2007
Dose and effect
Drug levels in an individual patient are dependant on many factors – compliance, absorption, drug half-life and metabolism. Whilst clinicians can establish a drug’s efficacy in some cases by looking for an improvement in symptoms, or with simple assessment of blood pressure or temperature, therapeutic drug monitoring (TDM) offers an additional level of information for patient management. This review of TDM examines its importance.
Treating the individual
Correlation between dose and effect is generally poor as individuals absorb and metabolise drugs differently. If a patient’s dose is too low then efficacy may be affected and drug resistance may develop. Conversely, if the patient’s dose is too high then toxicity can result.
Absorption of the cardiac drug digoxin, for example, varies significantly between individuals. This effect is further exacerbated by the drug’s formulation. If the dosage is too high, the patient may experience arrhythmia.
Patients also vary in their metabolism of particular drugs. It is recommended that prior to prescribing such drugs, the serum levels of enzymes involved in their metabolism are known. This is true for the immunosuppressant drug azathioprine, which is prescribed to prevent rejection of kidney transplants or to treat severe rheumatoid arthritis.
Tailoring dosage in this manner is especially important for drugs with a narrow therapeutic window.
Which drugs need monitoring?
There are several categories of drugs that may require monitoring (see table 1). In addition to the cardiac and immunosuppressant examples above, these also include anti-infective agents.
Many anti-infective agents have a wide therapeutic range which means that standard doses can safely be used; however there are exceptions. Constantly high concentrations of anti-microbial aminoglycosides, such as gentamicin, may potentially be toxic to the kidneys and ears. In addition, the dose varies with serum creatinine levels. On the other hand, persistently low concentrations of vancomycin can result in treatment failure.
A final word
On average it takes 5-6 half lives for a drug to reach a steady state. Clinicians should allow for this period to elapse before requesting first and repeat drug levels. Once this period has passed, TDM enables the clinician to accurately establish a drug’s efficacy in the individual patient providing an additional, and vital, level of information for patient management.
References:
- Lab Tests Online UK <www.labtestsonline.org.uk>
- Barron, J. ‘Are the Drugs Working?’, Capital Doctor, Dec 2006
- Thomson, A. ‘Why Do Therapeutic Drug Monitoring’, The Pharmaceutical Journal, Jul 2004
| Examples of Drugs That Require TDM | ||
|---|---|---|
| Drug Category | Examples of Therapeutic Drugs |
Treatment Use |
| Cardiac drugs | Digoxin, digitoxin | Congestive heart failure, arrhythmias |
| Antibiotics/ aminoglycosides |
Amikacin, gentamycin, tobramycin,vancomycin | Infections with bacteria that are resistant to less toxic antibiotics |
| Antiepileptics | Carbamazepine, phenobarbitol, phenytoin, valproate | Epilepsy, prevention of seizures |
| Bronchodilators | Theophylline, caffeine | Asthma, chronic obstructive pulmonary disease (COPD), neonatal apnoea (a breathing disorder) |
| Immunosuppressants | Cyclosporine, sirolimus, tacrolimus | Prevent rejection of transplanted organs |
| Anti-cancer drugs | Methotrexate | Various cancers, rheumatoid arthritis, psoriasis |
TDM adds particular value in the following situations:
- Monitoring drugs with a narrow therapeutic range (those which can easily be under- or overdosed)
- Absence of clinical markers of effect – such as measuring glucose to determine the effectiveness of diabetes drugs
- Poor correlation of effect with dose – eg cyclosporine
- Good correlation between plasma concentrations and effect
Abbott therapeutic drug monitoring
Past
Abbott has been the worldwide leader in therapeutic and abused drug testing
since 1981 when the TDx was launched – the first automated system for TDMs and
DOAs that revolutionised drug testing.
Present
A number of analysers, both immunoassay and clinical chemistry, are now
available from Abbott for TDM testing: TDx/FLx, IMx, AxSYM, ARCHITECT i2000SR
and c8000. Tacrolimus and sirolimus assays were recently launched
on the i2000SR.
Future
During 2007, we expect nine additional TDM assays to become available on the i2000SR.
