Bidirectional interaction of valproate and lamotrigine in healthy subjects*

Anderson, Gail D.; Yau, Martin K.T.; Gidal, Barry E.; Harris, Simon; Levy, René H.; Lai, Allen A.; Wolf, Karen B.; Wargin, William A.; Dren, Anthony T.

doi:10.1016/s0009-9236(96)90130-7

Cited by 115 publications

(54 citation statements)

References 27 publications

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“…This observation is similar to the findings of previous studies, with values for this parameter ranging from 0.004 to 0.031 L·h -1 ·kg -1 and a mean of approximately of 0.015 L·h -1 ·kg -1 [26][27][28][29][30][31] .…”

Section: Discussionsupporting

confidence: 92%

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Wang

Qin

et al. 2012

Acta Pharmacol Sin

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Aim: To establish a population pharmacokinetics (PPK) model for lamotrigine (LTG) in Chinese children with epilepsy in order to formulate an individualized dosage guideline. Methods: LTG steady-state plasma concentration data from therapeutic drug monitoring (TDM) were collected retrospectively from 284 patients, with a total of 404 plasma drug concentrations. LTG concentrations were determined using a HPLC method. The patients were divided into 2 groups: PPK model group (n=116) and PPK valid group (n=168). A PPK model of LTG was established with NON-MEM based on the data from PPK model group according to a one-compartment model with first order absorption and elimination. To validate the basic and final model, the plasma drug concentrations of the patients in PPK model group and PPK valid group were predicted by the two models. Results: The final regression model for LTG was as follows: CL (L/h)=1.01*(TBW/27.87) 0.635 *e -0.753*VPA *e 0.868*CBZ *e 0.633*PB , Vd (L)= 16.7*(TBW/27.87). The final PPK model was demonstrated to be stable and effective in the prediction of serum LTG concentrations by an internal and external approach validation. Conclusion: A PPK model of LTG in Chinese children with epilepsy was successfully established with NONMEM. LTG concentrations can be predicted accurately by this model. The model may be very useful for establishing initial LTG dosage guidelines.

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Section: Discussionsupporting

confidence: 92%

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Wang

Qin

et al. 2012

Acta Pharmacol Sin

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“…Alternatively, the extent of formation of a teratogenic valproate metabolite may be altered. In healthy, nonpregnant volunteers, Anderson et al (1996) showed that lamotrigine administration increased the clearance of valproate.…”

Section: Discussionmentioning

confidence: 99%

The teratogenic risk of antiepileptic drug polytherapy

et al. 2010

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Several publications have reported an increased risk of fetal malformation in the offspring of mothers who during pregnancy took more than one antiepileptic drug (AED) simultaneously as compared to those taking AED monotherapy (Tanganelli & Regesta, 1992;Olafsson et al., 1998;Arpino et al., 2000;Lowe, 2001;Hart, 2003;Morrow & Craig, 2003;Pack, 2006). A similar increased risk in patients taking polytherapy was not found in an earlier analysis of data from the Australian Register of AEDs in Pregnancy (Vajda et al., 2003). Here we have specifically reexamined the issue of the relative teratogenic risk of AED polytherapy in the larger cohort of women now enrolled on the register, with particular attention to the nature and dose of the drugs taken. Materials and Methods Analysis of data from the Australian Pregnancy RegisterThe Australian Register of Antiepileptic Drugs in Pregnancy has been collecting data concerning the use of AEDs in pregnant women since 1999. Recruitment is nationwide and voluntary, and contact with the register is by telephone. Potentially eligible women are informed about the register by a variety of methods, but most commonly by their treating medical practitioners, nurses, or allied health professionals, or by other pregnant women. Relevant details are obtained from pregnant women on recruitment (usually in the first or second trimester), at 7 months of pregnancy, in the first postnatal month, and at the end of the first postnatal year. Treating doctors are contacted to confirm medical details. Fetal malformations are classified according to the Birth Defects Registry of Victoria (Riley & Haliday, 1988). The register database was housed initially at St Vincent's Hospital, Melbourne, and subsequently at Monash University, Melbourne, and has been under the consecutive ethical oversight of the ethics committees of these institutions.For the purposes of this analysis the incidence of the malformations was determined on the basis of all information available at the end of the first postnatal month and the first postnatal year. The 1-year data were used for all analyses except for comparisons with the international literature, for which the 1-month data were also used.The data relevant to the present article were extracted from the register's Microsoft Access database into an Excel spreadsheet and then analyzed by confidence interval (CI)

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“…In the management of epilepsy, there does not appear mean half-life of lamotrigine is immediately increased to about 70 h and steady-state lamotrigine plasma concen-to be a correlation between lamotrigine blood levels and efficacy. trations are increased [45]. Therefore, when lamotrigine is added to ongoing treatment with valproate, the initial…”

Section: Lithium Studies In Bipolar Depressionmentioning

confidence: 99%

Clinical Studies on the Use of Lamotrigine in Bipolar Disorder

et al. 1998

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New mood stabilizers that possess efficacy in the depressed phase of bipolar disorder are needed. The use of marketed antidepressants puts bipolar patients at some increased risk for drug-induced hypomania/mania and rapid cycling. During the development of the antiepileptic, lamotrigine, the drug was observed to improve mood, alertness, and social interactions in some patients with epilepsy. These early observations provided the rationale for investigations into lamotrigine’s potential efficacy in bipolar disorder. There are now 14 open clinical reports involving a total of 207 lamotrigine-treated patients with bipolar disorder that suggest this drug possesses a broad spectrum of efficacy in the management of the depressed, hypomanic, manic, and mixed phases of bipolar disorder. In an attempt to replicate and extend these preliminary open-label prospective findings, a series of multicenter, double-blind, placebo-controlled studies evaluating the efficacy and dose-response relationships of lamotrigine in the various phases of the illness, including both acute and maintenance designs in both bipolar I and II disorder, is ongoing.

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Bidirectional interaction of valproate and lamotrigine in healthy subjects*

Abstract: As a consequence of the interaction between lamotrigine and sodium valproate, a dosage reduction of lamotrigine should be considered in patients taking a combination of valproate and lamotrigine.

Cited by 115 publications

References 27 publications

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

The teratogenic risk of antiepileptic drug polytherapy

Clinical Studies on the Use of Lamotrigine in Bipolar Disorder

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