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Type: Journal article
Title: Clinical study of lamotrigine and valproic acid in patients with epilepsy: Using a drug interaction to advantage?
Author: Morris, R.
Black, A.
Lam, E.
Westley, I.
Citation: Therapeutic Drug Monitoring, 2000; 22(6):656-660
Publisher: Lippincott Williams & Wilkins
Issue Date: 2000
ISSN: 0163-4356
Statement of
Raymond G. Morris, Andrew B. Black, Esther Lam, and Ian S. Westley
Abstract: Lamotrigine (LTG) is one of the newer antiepileptic drugs which has been shown to have a spectrum of drug interactions (including with other epilepsy drugs) that can have a pronounced effect on LTG kinetics. The present study examined the LTG metabolic inhibition dose-response relationship with valproic acid (VPA) in eight patients with epilepsy with a view to using this to benefit the patient. This could benefit the patient not only by attaining higher plasma LTG concentrations with "standard" dosages of LTG, but also possibly by achieving better seizure control through providing a less variable peak-to-trough fluctuation in LTG concentrations as a result of extending the half-life of LTG. The dosages of VPA trialed were 0, 200, 500, and 1,000 mg/d which resulted in a mean increase in LTG area under the curve of 83.7 +/- 14.7% at 200 mg VPA/d, to and 160 +/- 37.9% at 1,000 mg VPA/d. The presence of concomitant enzyme inducers in some patients did not influence the percentage increase from baseline in half-life observed, although clearly those on inducers started from a lower absolute half-life as a result of the induction. The effect was shown to be quite variable, particularly at the highest dosage of VPA tested (1,000 mg/d), suggesting that this effect could be best applied with the support of the therapeutic drug monitoring laboratory determining plasma LTG concentrations to allow individualization of the LTG dosage.
Keywords: Humans
Valproic Acid
Enzyme Inhibitors
Drug Therapy, Combination
Area Under Curve
Dose-Response Relationship, Drug
Drug Synergism
Middle Aged
Rights: © 2000 Lippincott Williams & Wilkins, Inc.
DOI: 10.1097/00007691-200012000-00003
Appears in Collections:Aurora harvest 2
Pharmacology publications

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