Test ID: TIAG
Tiagabine Concentration, Serum
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
This test is used for monitoring tiagabine therapy. Because tiagabine has a wide therapeutic index and dose-dependent toxicity, routine drug monitoring is not indicated in all patients. Drug monitoring is indicated when initiating concomitant therapy with antiepileptic drug that induce hepatic enzymes and when the patient does not respond to treatment to ascertain whether treatment failure is due to noncompliance or nonresponse to the drug.
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Tiagabine (Gabitril) is indicated as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures. It is frequently administered to patients receiving at least 1 concomitant antiepileptic drug (AED).(1) Tiagabine is a selective blocker of gamma-aminobutyric acid (GABA) uptake into presynaptic neurons. Tiagabine binds to recognition sites associated with the GABA uptake carrier. By this action, tiagabine blocks GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surface of post-synaptic cells.(1,2)
Tiagabine has an elimination half-life of 7 to 9 hours in normal volunteers. In patients receiving enzyme-inducing AEDs, the elimination half-life decreases to 4 to 7 hours. Phenytoin, phenobarbital, and carbamazepine are AED enzyme inducers; valproate and gabapentin are not. Tiagabine is not considered to be an enzyme-inducing AED.(2,6)
Tiagabine reaches peak serum concentration approximately 45 minutes following an oral dose in the fasting state. Tiagabine is well absorbed with food slowing the absorption rate but not altering the extent of absorption (high fat diet prolongs peak serum concentrations to about 2.5 hours). Tiagabine is >95% absorbed, with oral bioavailability of about 90%. Tiagabine pharmacokinetics are linear over the typical dose range of 2 to 24 mg. Steady-state is achieved within 2 days. Tiagabine is 96% bound to human plasma proteins, mainly to serum albumin and alpha-1-acid glycoprotein. Coadministration with valproate reduces protein binding to 94%, increasing the free fraction of tiagabine by 40%.(3,6)
Based on in vitro data, tiagabine is likely to be metabolized by the 3A isoform subfamily of hepatic cytochrome P450 (CYP 3A), although contributions to the metabolism from CYP 1A2, CYP 2D06, or CYP 2C19 have not been excluded.(3)
Method Name A short description of the method used to perform the test
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Tiagabine (Gabitril)
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Collection Container/Tube: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions:
1. Serum for a peak concentration should be drawn 1 hour after administration of oral tiagabine. Serum for a trough concentration is usually drawn 30 minutes before dose.
2. Label specimen appropriately (peak or trough).
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross reject |
| Lipemia | Mild OK; Gross reject |
| Icterus | Mild OK; Gross reject |
| Other | Serum gel tube |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Serum Red | Frozen (preferred) | 7 days |
| Refrigerated | 48 hours |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Tiagabine (Gabitril) is indicated as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures. It is frequently administered to patients receiving at least 1 concomitant antiepileptic drug (AED).(1) Tiagabine is a selective blocker of gamma-aminobutyric acid (GABA) uptake into presynaptic neurons. Tiagabine binds to recognition sites associated with the GABA uptake carrier. By this action, tiagabine blocks GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surface of post-synaptic cells.(1,2)
Tiagabine has an elimination half-life of 7 to 9 hours in normal volunteers. In patients receiving enzyme-inducing AEDs, the elimination half-life decreases to 4 to 7 hours. Phenytoin, phenobarbital, and carbamazepine are AED enzyme inducers; valproate and gabapentin are not. Tiagabine is not considered to be an enzyme-inducing AED.(2,6)
Tiagabine reaches peak serum concentration approximately 45 minutes following an oral dose in the fasting state. Tiagabine is well absorbed with food slowing the absorption rate but not altering the extent of absorption (high fat diet prolongs peak serum concentrations to about 2.5 hours). Tiagabine is >95% absorbed, with oral bioavailability of about 90%. Tiagabine pharmacokinetics are linear over the typical dose range of 2 to 24 mg. Steady-state is achieved within 2 days. Tiagabine is 96% bound to human plasma proteins, mainly to serum albumin and alpha-1-acid glycoprotein. Co-administration with valproate reduces protein binding to 94%, increasing the free fraction of tiagabine by 40%.(3,6)
Based on in vitro data, tiagabine is likely to be metabolized by the 3A isoform subfamily of hepatic cytochrome P450 (CYP 3A), although contributions to the metabolism from CYP 1A2, CYP 2D06, or CYP 2C19 have not been excluded.(3)
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.
Peak: 110-520 ng/mL
Trough: 5-35 ng/mL
Interpretation Provides information to assist in interpretation of the test results
Trough tiagabine serum concentrations are in the range of 5 to 35 ng/mL in most patients receiving therapeutic doses. Tiagabine serum concentration is proportional to dose.(2,8) A single 4-mg dose administered to a child produced peak serum concentration in the range of 52 to 108 ng/mL.(5) At steady-state, an adult receiving 40 mg per day is expected to have peak serum concentration in the range of 110 to 260 ng/mL, and an adult receiving 80 mg per day is expected to have peak serum concentration in the range of 220 to 520 ng/mL. Serum concentrations >800 ng/mL indicates excessive dosing associated with adverse effects such as asthenia, ataxia, difficulty concentrating, and depression.
In healthy adults administered tiagabine, steady-state peak serum concentrations within 1 hour of dosing are typically in the following ranges:(2)
-Peak serum concentration (4 mg q.i.d.): 36 to 92 ng/mL
-Peak serum concentration (8 mg q.i.d.): 72 to 184 ng/mL
Pediatric patients (3-10 years) reach peak concentration at approximately 2.4 hours.(5)
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Drugs that may interfere with the internal standard include verapamil, lorazepam, and bupivacaine. Coadministration of these drugs will generate an artifactually decreased tiagabine concentration.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Product information: Gabitril Filmtab, tiagabine hydrochloride. Abbott Laboratories, North Chicago, IL, 1997
2. So EL, Wolff D, Graves N, et al: Pharmacokinetics of tiagabine as add-on therapy in patients taking enzyme-inducing antiepilepsy drugs. Epilepsy Res 1995;22:221-226
3. Benedetti MS: Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies. Fundam Clin Pharmacol 2000;14:301-319
4. Perucca E: The clinical pharmacokinetics of the new antiepileptic drugs. Epilepsia 1999;40:S7-S13
5. Gustavson LE, Soellner SW, Granneman GR, et al: A single-dose study to define tiagabine pharmacokinetics in pediatric patients with complex partial seizures. Neurology 1997;48:1032-1037
6. Cato A, Gustavson LE, El-Shourbay, Kelly EZ: Effect of renal impairment on the pharmacokinetics and tolerability of tiagabine. Epilepsia 1998;39:43-47
7. Wiley Cl, Enger RJ, Charlson JC, Moyer TP: Unpublished Mayo information
8. Thompson MS, Groes L, Agerse H, Kruse T: Lack of pharmacokinetic interaction between tiagabine and erythromycin. J Clin Pharmacol 1998;38:1051-1056
Method Description Describes how the test is performed and provides a method-specific reference
Drug and internal standard are extracted from serum. The extract is quantified using liquid chromatography-tandem mass spectrometry.(Wiley Cl, Enger RJ, Charlson JC, Moyer TP: unpublished Mayo information)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday, Wednesday
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
80299
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 82524 | Tiagabine, S | 21565-7 |
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