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Unit Code 80999:
Lamotrigine, Plasma or Serum

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Useful For

Monitoring serum concentration of lamotrigine

 

Assessing compliance

 

Adjusting lamotrigine dose in patients receiving other anticonvulsant

drugs which interact pharmacokinetically with lamotrigine.

                                                                     

Clinical Information

Lamotrigine (Lamictal) is an antiepileptic drug recently approved

by the Food and Drug Administration that is effective as adjunctive

therapy in treating resistant partial and generalized toxic clonic

seizures. It is also effective in some patients with Lennox-Gastaut

syndrome and in children with multiple seizure types.

 

Adverse effects are generally mild; they are usually central nervous

system-related and include:

      - Somnolence

      - Dizziness

      - Ataxia

      - Diplopia

      - Blurred vision

 

The mechanism of action is thought to be related to lamotrigine's

ability to stabilize presynoptic neuronal membranes by blocking

voltage dependent Na( ) channels, thereby inhibiting the release of

excitatory neurotransmitters, mainly glutamate.

 

Oral bioavailability exceeds 90%, and lamotrigine circulates 55%

bound to plasma proteins. Approximately 70% of an oral dose is

recovered in urine mostly as the glucuronide conjugate. The drug

does not appear to produce any pharmacologically active

metabolites. The mean elimination half-life is 30 hours

(SD=10 hours). However, the half-life is approximately halved

with concurrent use of phenytoin or carbamazepine and

approximately doubled when co-administered with valproic acid.

Conversely, addition of lamotrigine causes little change in the

serum concentration of other anticonvulsant drugs with the

possible exception of carbamazepine-10,11-epoxide

(the active metabolite of carbamazepine) which may increase

in concentration.

                                                                     

 

Reference Values

Patients receiving doses within the recommended range (50-400

mg/day) usually have lamotrigine concentrations between 1and 4

ug/mL.

Interpretation

The serum concentration should be interpreted in the

context of the patient's clinical response and may provide useful

information in patients showing poor response (noncompliance?)

or adverse effects, particularly when lamotrigine is

co-administered with other anticonvulsant drugs. While most

patients show response to the drug when the trough concentration

is in the range of 1-4 ug/mL, and many patients show signs of

toxicity when the peak serum concentration is >20 ug/mL,

some patients can tolerate peak concentrations as high as 70

ug/mL.

 

  

Cautions

Chlorpropamide, flecainide, and methaqualone

interfer with this test.

 

To obtain an accurate serum lamotrigine concentration, the patient

should not be taking these drugs.

 

 

Clinical Reference

1.   Goa KL, Ross SR, Chrisp P:  Lamotrigine: A review of its

      pharmacological properties and clinical efficacy in epilepsy.

      Drugs 1993;46:152-176

 

2.   Upton N:  Mechanisms of action of new antiepileptic drugs:

      rational design and serendipitous findings.  Trends Pharmacol Sci

      1994;15:456-463

 

3.   Cohen AF, Land GS, Breimer DD, et al:  Lamotrigine, a new

      anticonvulsant:  pharmacokinetics in normal humans. Clin Pharmacol

      Ther 1987;42:535-541

 

 


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