Test Catalog

Test Id : PNYG

Phenytoin, Total and Phenobarbital Group, Serum

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

Monitoring for appropriate therapeutic concentration of phenytoin and phenobarbital

 

Assessing compliance or toxicity

Profile Information
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

Test Id Reporting Name Available Separately Always Performed
PNYA Phenytoin, Total, S Yes Yes
PBR Phenobarbital, S Yes Yes

Method Name
A short description of the method used to perform the test

Kinetic Interaction of Microparticles in a Solution (KIMS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Phenytoin, Tot and Phenobarbital, S

Aliases
Lists additional common names for a test, as an aid in searching

Barbita (Phenobarbital)

Dilantin (Do Phenytoin, Total unless Free specified)

Dilantin (Phenytoin)

Dilantin + Phenobarb ORDER P_PB

Diphenylhydantoin

Diphenylhydantoin + Phenobarb ORDER P_PB

DPH

Luminal (Phenobarbital)

PBR

Phenobarb + Mephobarbital ORDER MEPHS

Phenobarb + Phenytoin Total ORDER P_PB

Phenobarb + Primidone ORDER PBPR

Phenobarbital

Phenytoin (Dilantin)

Phenytoin Total + Phenobarb ORDER P_PB

Phenytoin, Free and Total ORDER PNYFR

Phenytoin, Total and Free ORDER PNYFR

Solfoton (Phenobarbital)

Specimen Type
Describes the specimen type validated for testing

Serum

Serum Red

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

One serum specimen (0.5 mL of serum) may be sent if using a red top tube.

 

Serum for Phenytoin:

Container/Tube: Red top

Specimen Volume: 0.5 mL

Collection Instructions: Red-top tubes should be centrifuged and aliquoted within 2 hours of collection.

 

Serum for Phenobarbital:

Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Specimen Volume: 0.5 mL

Collection Instructions:

1. Serum gel tubes should be centrifuged within 2 hours of collection.

2. Red-top tubes should be centrifuged and aliquoted within 2 hours of collection.

Forms

If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.25 mL for 2 specimens; 0.25 mL for 1 serum red top

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 14 days
Frozen 28 days
Ambient 72 hours
Serum Red Refrigerated (preferred) 7 days
Frozen 14 days
Ambient 7 days

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

Monitoring for appropriate therapeutic concentration of phenytoin and phenobarbital

 

Assessing compliance or toxicity

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

Phenytoin, Total:

Phenytoin is the drug of choice to treat and prevent tonic-clonic and psychomotor seizures. If phenytoin alone will not prevent seizure activity, coadministration with phenobarbital is usually effective.

 

Initial therapy with phenytoin is started at doses of 100 to 300 mg/day for adults or 4 mg/kg/day for children. Because absorption is variable and the drug exhibits zero-order (nonlinear) kinetics, dose must be adjusted within 5 days using blood concentration to guide therapy. Oral bioavailability ranges from 80% to 95% and is diet-dependent.

 

Phenytoin exhibits zero-order pharmacokinetics; the rate of clearance of the drug is dependent upon the concentration of drug present. Therefore, phenytoin does not have a classical half-life like other drugs, since it varies with blood concentration. At a blood concentration of 15 mcg/mL, approximately half the drug in the patient's body will be eliminated in 20 hours. As the blood concentration drops, the rate at which phenytoin is excreted increases.

 

Phenytoin has a volume of distribution of 0.65 L/kg, and is highly protein bound (90%), mostly to albumin. Some drug side-effects occur in the therapeutic range; these include gingival hyperplasia, hyperglycemia, and skin rash.

 

Phenytoin pharmacokinetics are significantly affected by a number of other drugs. As noted above, phenytoin and phenobarbital are frequently coadministered. Induction of the cytochrome P450 enzyme system by phenobarbital will increase the rate at which phenytoin is metabolized and cleared. At steady-state, enzyme induction will increase the rate of clearance of phenytoin such that the dose must be increased approximately 30% to maintain therapeutic levels.

 

Uremia has a similar effect on phenytoin protein binding. In uremia, by-products of normal metabolism accumulate and bind to albumin, displacing phenytoin which causes an increase in the free fraction.

 

Valproic acid, an antiepileptic frequently coadministered with phenytoin, competes for the same binding sites on albumin as phenytoin. Valproic acid displaces phenytoin from albumin, reducing the bound fraction and increasing the free fraction. The overall effect of coadministration of a therapeutic dose of valproic acid is that the total concentration of phenytoin decreases due to increased clearance but the free fraction increases; the free concentration of phenytoin, which is the active form remains virtually the same. Thus, no dosage adjustment is needed when valproic acid is added to maintain the same pharmacologic effect, but the total concentration of phenytoin decreases.

 

In contrast to the valproic acid situation, in renal failure, there is not the same opportunity for the free phenytoin fraction to be cleared. The end result is that both the total and free concentration of phenytoin increase, with the free concentration increasing faster than the total. Dosage must be reduced to avoid toxicity.

 

The free phenytoin level is the best indicator of adequate therapy in renal failure.

 

Toxicity is a constant possibility because of the manner in which phenytoin is metabolized. Small increases in dose can lead to very large increases in blood concentration, resulting in early signs of toxicity such as nystagmus, ataxia, and dysarthria. Severe toxicity occurs when the blood concentration is >30 mcg/mL and is typified by tremor, hyperreflexia, and lethargy. The outcome of phenytoin toxicity is not as serious as phenobarbital because phenytoin is not a central nervous system sedative.

 

Phenobarbital:

Phenobarbital is a general central nervous system (CNS) suppressant that has proven effective in the control of generalized and partial seizures. It is frequently coadministered with phenytoin for control of complex seizure disorders and with valproic acid for complex parietal seizures.

 

Phenobarbital is administered in doses of 60 to 300 mg/day in adults or 3 to 6 mg/kg/day in children.

 

Phenobarbital is slowly but completely absorbed, with bioavailability in the range of 100%. It is approximately 50% protein bound with a volume of distribution of 0.5 L/kg. Phenobarbital has a long half-life of 96 hours, with no known active metabolites.

 

Sedation is common at therapeutic concentrations for the first 2 to 3 weeks of therapy, but this side effect disappears with time.

 

Toxicity due to phenobarbital overdose is characterized by CNS sedation and reduced respiratory function. Mild symptoms characterized by ataxia, nystagmus, fatigue, or attention loss, occur at blood concentrations >40 mcg/mL. Symptoms become severe at concentrations > or =60 mcg/mL. Toxicity becomes life-threatening at concentrations >100 mcg/mL. Death usually occurs due to respiratory arrest when pulmonary support is not supplied manually.

 

There are no known drug interactions that significantly affect the pharmacokinetics of phenobarbital; conversely, phenobarbital affects the pharmacokinetics of other drugs significantly because it induces the synthesis of enzymes associated with the hepatic cytochrome P450 metabolic pathway.

 

Acute intermittent porphyria attacks may be induced by phenobarbital stimulation of hepatic cytochrome P450.

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.

PHENYTOIN, TOTAL

Therapeutic: 10.0-20.0 mcg/mL

Critical value: > or =30.0 mcg/mL

 

PHENOBARBITAL

Therapeutic: 10.0-40.0 mcg/mL:

Critical value: > or =60.0 mcg/mL

Interpretation
Provides information to assist in interpretation of the test results

The therapeutic ranges for adults taking phenytoin have been established at 10 to 20 mcg/mL for total phenytoin (bound plus unbound). The therapeutic range for phenobarbital is10 to 40 mcg/mL. Within these ranges, most people will respond to the drugs without symptoms of toxicity. However, response and side effects will be individual. Dosage determinations and adjustments must be evaluated on a case-by-case basis. A free (unbound) phenytoin level may also need to be ordered when a person has kidney failure, liver disease, hypoalbuminemia, or is taking other medications like aspirin, naproxen, or ibuprofen, in which situation the percentage of free (active) phenytoin may be increased.

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

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

Phenytoin, Total:

1. Richens A: Clinical pharmacokinetics of phenytoin. Clin Pharmacokinet 1979;4:153-169

2. Moyer TP: Therapeutic drug monitoring. In Tietz Textbook of Clinical Chemistry. Fourth edition. Edited by CA Burtis, ER Ashwood. WB Saunders Company, Philadelphia, 2005, pp 1237-1285

 

Phenobarbital:

Foero O, Kastrup KW, Nielsen EL, et al: Successful prophylaxis of febrile convulsions with phenobarbital. Epilepsia 1972;13:279-285

Method Description
Describes how the test is performed and provides a method-specific reference

Phenytoin, Total:

The assay is based on the kinetic interaction of microparticles in a solution (KIMS). Phenytoin antibody is covalently coupled to microparticles and the drug derivative is linked to a macromolecule. The kinetic interaction of microparticles in solutions is induced by binding of drug-conjugate to the antibody on the microparticles and is inhibited by the presence of phenytoin in the sample. A competitive reaction takes place between the drug conjugate and phenytoin in the serum sample for binding to the phenytoin antibody on the microparticles. The resulting kinetic interaction of microparticles is indirectly proportional to the amount of drug present in the sample.(Package insert: Roche Phenytoin reagent, Roche Diagnostic Corp, Indianapolis, IN)

 

Phenobarbital:

The assay is based on the kinetic interaction of microparticles in a solution (KIMS). Phenobarbital antibody is covalently coupled to microparticles and the drug derivative is linked to a macromolecule. The kinetic interaction of microparticles in solutions is induced by binding of drug-conjugate to the antibody on the microparticles and is inhibited by the presence of phenobarbital in the sample. A competitive reaction takes place between the drug conjugate and phenobarbital in the serum sample for binding to the phenobarbital antibody on the microparticles. The resulting kinetic interaction of microparticles is indirectly proportional to the amount of drug present in the sample.(Package insert: Roche Phenobarbital reagent, Roche Diagnostic Corp, Indianapolis, IN)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Sunday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

Same day/1 day

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

1 week

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test has been cleared or approved by the U.S. Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

80184-Phenobarbital

80185-Phenytoin, total

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
PNYG Phenytoin, Tot and Phenobarbital, S In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
PBR Phenobarbital, S 3948-7
PNYA Phenytoin, Total, S 3968-5

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports