Therapeutic drug monitoring (TDM) is defined as measurement of drug levels in the biological fluids usually blood (serum or plasma). It has been carried out in saliva, urine, sweat, tear fluids, etc. It is carried out for specific drugs at various time intervals in order to maintain a relatively constant concentration of the particular drug in the bloodstream and to optimize drug therapy. The main focus of TDM is on drugs with narrow therapeutic range. Apart from this, it also plays a significant role for drugs having large inter-individual variations; relatively toxic drugs used in concomitant disease conditions, for escalation of dose, drugs showing wide variation in their metabolism, major organ failure, poisoning cases, failure of therapeutic response, to enhance patient compliance, etc. It is very important in such situations in which the drugs are to be taken on chronic or life-long basis (chronic disease conditions such as bipolar disorder, organ transplant rejection, neurological disorders, etc.). The timing and frequency of blood collection after the medication and correct interpretation of results of analysis and their correlation with clinical features ensures the best therapeutic outcome.
• Drugs whose efficacy is difficult to establish clinically, like Phenytoin.
• Drugs with a narrow therapeutic index. Examples: Lithium, phenytoin, digoxin.
• Patients who have impaired clearance of a drug with a narrow therapeutic index. e.g., Patients with renal failure have decreased clearance of digoxin and therefore are at a higher risk of toxicity.
• Drugs whose toxicity is difficult to distinguish from a patient’s underlying disease. e.g., Patients with chronic obstructive pulmonary disease treated with theophylline.
1. Drugs whose pharmacological effects can easily be used to dose titration, like oral hypoglycemic agents, anti-hypertensive drugs.
2. When easier and/or cheaper methods/alternatives to TDM are available to titrate the drug like International normalized ratio(INR) for warfarin.
1. Sample should be collected after steady state has been reached (5 half-lives), unless TDM is intended to predict toxicity after single dose.
2. Usually “trough” concentrations are measured by taking the sample just before the subsequent dose.
3. Drugs whose half-lives are much shorter than the dosing interval, the peak and trough levels may be indicated to evaluate the dosage of drugs. e.g., Gentamicin.
TDM could be affected because of one or more of the factors relating to pharmacokinetics of the drug, or drug administration, or sample collection. Renal and hepatic alterations to half-life must also be considered. Laboratory variations also affect the TDM.
The following table summarizes the therapeutic concentration range of various drugs:
S. No. | Pharmacological category | Drugs | Therapeutic drug conc. range |
1. | Drugs acting on cardiovascular system | Amiodarone Digoxin Procainamide | 1.0-2.5 µg/ml |
2. | Antibiotics | Gentamycin Amikacin Vancomycin Tobramycin | 5.0-10.0 µg/ml |
3. | Antiepileptics | Phenobarbital Phenytoin Valproic acid Carbamazepine Ethosuximide Gabapentin Lamotrigine | 15.0-40.0 µg/ml |
4. | Immunosuppressants | Cyclosporine Tacrolimus Sirolimus Mycophenolate mofetil | 50.0-300.0 µg/ml |
5. | Psychopharmacological agents | Lithium Imipramine Amitriptyline Nortriptyline Desipramine Clozapine | 0.8-1.2 mEq/l |
6. | Anti-infective | Cycloserine Ethambutol Pyrazinamide Streptomycin | 20-35 µg/ml |
TDM gives useful information regarding individual variations in drug utilisation patterns as a consequence of altered physiological state or disease process and thus, provides the clinician a better insight into the factors determining the patient’s response to drug therapy.