Test Catalog

Test ID: CARF    
Carbamazepine, Free, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Monitoring unbound or free carbamazepine levels in patients where the total carbamazepine result is within the therapeutic range but the patient is experiencing side effects


Monitoring carbamazepine (free) therapy in uremic patients

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Carbamazepine (Tegretol) is an effective treatment for complex partial seizures, with or without generalization to tonic-clonic seizures.(1) It is frequently administered in conjunction with other antiepileptic agents, such as phenytoin and valproic acid.(2) Under normal circumstances, the carbamazepine that circulates in blood is 70% to 80% protein-bound.(3) Only the free drug is able to enter the interstitial space in the brain where the pharmacological effects occur.(4)


Patient management is best guided by monitoring free serum concentrations when protein binding is altered. Altered protein binding occurs in patients with hypoalbuminemia observed during pregnancy, in the malnourished, and liver disease. In patients with renal disease, uremia may develop whose byproducts can displace bound carbamazepine increasing the unbound fraction. Administration of drugs that are able to compete for serum protein binding sites may also increase the unbound fraction of carbamazepine. Since neurologic activity and toxicity of carbamazepine are directly related to the circulating free fraction of drug, adjustment of dosage based on knowledge of the free carbamazepine concentration may be more useful in these patient populations.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Therapeutic concentration: 1.0-3.0 mcg/mL

Critical value: > or =4.0 mcg/mL

Interpretation Provides information to assist in interpretation of the test results

In patients with normal renal function, optimal response is often associated with free (unbound) carbamazepine levels above 1.0 mcg/mL, and toxicity may occur when the free carbamazepine is greater than or equal to 4.0 mcg/mL.


Under normal circumstances, the carbamazepine that circulates in blood is 75% protein-bound. Therapies or conditions such as uremia that displace carbamazepine from protein cause a higher free (unbound) fraction of the drug circulating in blood. In uremia, the free carbamazepine level may be a more useful guide for dosage adjustments than the total level. In patients with severe uremia, subtherapeutic total carbamazepine levels in the range of 1.0 to 2.0 mcg/mL may be associated with therapeutic free carbamazepine levels. Toxicity may occur when the free carbamazepine level is greater than or equal to 4.0 mcg/mL (even though the total carbamazepine concentration is <15.0 mcg/mL).


As with the serum levels of other anticonvulsant drugs, total and free carbamazepine levels should be correlated with the patient's clinical condition. Serum levels are best used as a guide in dose adjustment.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Fresh serum with normal protein content is required for optimal analysis.


Specimens subjected to significant heat or other factors that cause protein denaturation may demonstrate an artifactually increased free carbamazepine level.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Svinarov DA, Pippenger CE: Relationships between carbamazepine-diol, carbamazepine-epoxide, and carbamazepine total and free steady-state concentrations in epileptic patients: the influence of age, sex, and comedication. Ther Drug Monit 1996;18:660-665

2. Bernus I, Dickinson RG, Hooper WD, Eadie MJ: The mechanism of the carbamazepine-valproate interactions in humans. Br J Clin Phamacol 1997;44:21-27

3. Dasgupta A, Volk A: Displacement of valproic acid and carbamazepine from protein binding in normal and uremic sera by tolmetin, ibuprofen, and naproxen: presence of inhibitor in uremic serum that blocks valproic acid-naproxen interactions. Ther Drug Monit 1996;18:284-287

4 Patsalos PN, Berry DJ, Bourgeois BF, et al: Antiepileptic drugs-best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia 2008;49(7):1239-1276