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Unexplained spikes in lamotrigine serum concentration: nonlinear elimination?
P Ramey1, M R Osborn1, K M Lowen1
1Department of Neurology, Vanderbilt University, Nashville, TN, USA.
Acta Neurologica Scandinavica
|April 1, 2016
Summary
Lamotrigine (LTG) can exhibit nonlinear pharmacokinetics at high serum concentrations, leading to unexpected toxicity. Close monitoring of LTG levels is crucial, especially when levels exceed 10 mg/l.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Neuroscience
Background:
- Lamotrigine (LTG) is typically considered to have linear pharmacokinetics.
- Linear kinetics implies that drug elimination rate is proportional to blood concentration.
- This means dose changes should result in proportionate serum concentration changes.
Observation:
- This study investigated unexpected increases in LTG serum concentrations.
- Twenty-two patients developed LTG toxicity with levels >20 mg/l, despite prior tolerance.
- In most cases, the dramatic LTG level increase was unexplained or disproportionate to dose adjustments.
Findings:
- Elevated LTG serum concentrations (>20 mg/l) can occur unexpectedly.
- Nonlinear elimination kinetics may be present in some individuals at higher LTG serum concentrations.
- Factors like valproate addition or postpartum changes can influence LTG levels.
Implications:
- Unexpected LTG toxicity can arise from nonlinear pharmacokinetics.
- Therapeutic drug monitoring of LTG is essential, particularly for patients with baseline levels >10 mg/l.
- Clinicians should be vigilant for new symptoms suggestive of LTG toxicity.
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