Carbamazepine, Free and Total, Serum
Monitoring carbamazepine 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. It is frequently administered in conjunction with other antiepileptic agents, such as phenytoin and valproic acid.
Under normal circumstances, the carbamazepine that circulates in blood is 75% protein bound. In severe uremia, carbamazepine may be displaced from protein, resulting in a higher free (unbound) fraction of the drug circulating in blood. Since neurologic activity and toxicity are directly related to the circulating free fraction of drug, adjustment of dosage based on knowledge of the free carbamazepine level may be useful in patients with severe uremia.
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: 4.0-12.0 mcg/mL
Toxic concentration: > or =15.0 mcg/mL
Therapeutic concentration: 1.0-3.0 mcg/mL
Toxic concentration: > or =4.0 mcg/mL
In patients with normal renal function, optimal response is often associated with free (unbound) carbamazepine levels >1.0 mcg/mL, and toxicity may occur when the free carbamazepine is > or =4.0 mcg/mL.
In uremic patients, 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 levels. Toxicity may occur in these patients when the free carbamazepine level is > or =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. They 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, although serum stored at 4 degrees C for <7 days is acceptable.
Specimens subjected to significant heat or other factors that cause protein denaturation demonstrate an artifactually increased free carbamazepine.
Clinical Reference Provides recommendations for further 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. Moyer TP: Therapeutic drug monitoring. In Tietz Textbook of Clinical Chemistry. Edited by CA Burtis, ER Ashwood. Fourth edition. Philadelphia, PA. WB Saunders Company 2005 pp 1237-1285
5. 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