Lamotrigine, a new anticonvulsant: Pharmacokinetics in normal humans

Cohen, Adam F.; Land, G.; Breimer, D. D.; Yuen, W. C.; Winton, C; Peck, A. W.

doi:10.1038/clpt.1987.193

Cited by 264 publications

(171 citation statements)

References 7 publications

Supporting

Mentioning

152

Contrasting

Unclassified

Order By: Relevance

“…Including the quantitative TBW covariate, LTG CL in the final model proposed was 0.039 L·h -1 ·kg -1 , which is higher than the values of approximately 0.021 to 0.035 L·h -1 ·kg -1 that were reported in PK studies evaluating small numbers of adult patients and healthy adult volunteers using standard approaches (2-stage methods with a 1-compartment model) [8][9][10]24] . Our study has shown a nonlinear increase of the CL and V d of LTG with an increase in total body weight.…”

Section: Discussionmentioning

confidence: 97%

“…The traditional method for calculating individual PK parameters was to collect multiple (up to [7][8][9][10] blood samples from a single patient at different times after a single dose. This method was not always accepted by patients, especially children.…”

Section: Original Articlementioning

confidence: 99%

“…A one-compartment, open kinetic model with first-order absorption and elimination (specified to NONMEM by the ADVAN2 and TRANS2 routines) was assumed according to the available bibliographic information [7][8][9][10] . Because the LTG steady-state trough plasma concentration data collected did not provide information about the extent and rate of absorption processes, the bioavailability (F) and absorption rate (K a ) were fixed at 1.0 and 1.0 h -1 , respectively [7] .…”

Section: Pharmacokinetic Modelingmentioning

confidence: 99%

See 2 more Smart Citations

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Wang

Qin

et al. 2012

Acta Pharmacol Sin

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Original Articlementioning

confidence: 99%

Section: Pharmacokinetic Modelingmentioning

confidence: 99%

See 1 more Smart Citation

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Wang

Qin

et al. 2012

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…Two reports indicate that induction of glucuronidation pathways by oxcarbazepine may affect the metabolism of lamotrigine (May et al, 1999;Kramer et al, 2003) and another describes higher MHD concentrations in the presence of lamotrigine compared to oxcarbazepine monotherapy (Guenault et al, 2003). Drug interactions may also be theoretically possible due to the potential inhibition of glucuronidation, which is the first-step of the metabolism and excretion pathway of the active metabolite of oxcarbazepine 10-monohydroxy (MHD) (May et al, 2003) as well as the most important metabolic transformation inactivating lamotrigine (Cohen et al, 1987;Lloyd et al, 1994).…”

Section: Lamotriginementioning

confidence: 99%

Lack of Pharmacokinetic Interaction between Oxcarbazepine and Lamotrigine

Theis

Sidhu

Palmer

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Epilepsy and bipolar disorder are commonly treated by combination drug therapy, such as lamotrigine and oxcarbazepine. To ensure the safety of this combination, information on pharmacokinetics and tolerability must be available. The objective of study was to evaluate the pharmacokinetics and tolerability of coadministered lamotrigine and oxcarbazepine in healthy subjects. This randomized, single-blind, parallel-group study comprised three cohorts: lamotrigine (200 mg daily) plus oxcarbazepine (600 mg twice daily), lamotrigine (200 mg daily) plus placebo, and oxcarbazepine (600 mg twice daily) plus placebo. Serial blood samples were collected at steady state to determine serum concentrations of lamotrigine and plasma concentrations of oxcarbazepine and its active metabolite 10-monohydroxy metabolite (MHD). Pharmacokinetic parameters were determined by noncompartmental methods. Tolerability was monitored through adverse event reports, clinical laboratory results, vital signs, and electrocardiograms. A total of 47 male volunteers received study drugs. At steady state, lamotrigine AUC and C max were not significantly affected by oxcarbazepine cotherapy, nor were MHD AUC (0)(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and C max significantly affected by lamotrigine cotherapy. The most common adverse events, headache, dizziness, nausea, and somnolence, occurred more frequently during lamotrigine and oxcarbazepine combination therapy than during the monotherapy. No significant changes in clinical laboratory parameters, vital signs, or electrocardiograms were reported. In conclusion, the combination of lamotrigine and oxcarbazepine does not require dose adjustments based on pharmacokinetic data. However, it is important to recognize that the combination therapy was associated with more frequent adverse events.

show abstract

“…According to a randomisation code, 12 subjects received either lamotrigine 300 mg or lactose placebo given as matching capsules. The intranasal CO 2 test was performed again 2 h after treatment to coincide approximately with peak plasma lamotrigine concentrations [8]. There was an interval of at least 2 weeks between treatments.…”

Section: Methodsmentioning

confidence: 99%

Effects of lamotrigine on pain‐induced chemo‐somatosensory evoked potentials

Klamt¹,

Posner

1999

Anaesthesia

View full text Add to dashboard Cite

SummaryLamotrigine, a sodium channel blocker that selectively inhibits the neuronal release of glutamate, has been shown to produce analgesia in acute and chronic pain models in rats without causing noticeable sedation. After oral administration it also reduces pain scores, as assessed by the cold pain test, in volunteers. The purpose of this study was to determine the analgesic effect of lamotrigine given by mouth to healthy volunteers as evidenced by alterations in chemosomatosensory evoked potentials. The following factors were measured: latency to N 1 and P 100 peak (ms); amplitude between the N 1 and P 100 peak (mV); visual analogue pain intensity scores. A double-blind, randomised and crossover design was used in which 12 volunteers received either placebo or lamotrigine 300 mg on separate occasions as determined by the randomisation schedule. Volunteers were tested before and 2 h after the treatment. The plasma lamotrigine concentration was measured immediately after the end of the experimental sessions. Lamotrigine produced a significantly higher latency to P 100 values at 2 h postdrug than placebo (p < 0.05) but had no significant effects on the other factors. Although plasma concentrations were similar to those observed in the cold pain test, we conclude that lamotrigine 300 mg by mouth had no analgesic effect in this acute pain model. Preto -SP, Brazil. CEP 14010-190 Accepted: 16 March 1998 Lamotrigine is a novel antiepileptic drug indicated for treatment of partial and generalised tonic clonic seizures. It is thought to act primarily by stabilising the presynaptic neuronal membrane by blocking voltage-dependent Na þ channels, thereby preventing the pathological release of excitatory neurotransmitters, principally glutamate [1-3]. Nakamura-Craig and Follenfant [4,5] have shown that oral administration of lamotrigine produces analgesia in acute (subplantar injection of PGE 2 ) and chronic (diabetic neuropathy and loose sciatic ligation) models of hyperalgesia in rats. A pilot study with volunteers using the coldpain test indicated that a single oral dose of lamotrigine 300 mg caused a significant reduction in subjective pain (unpublished data).Short painful chemical (CO 2 ) stimuli applied to the nasal mucosa elicit responses (late nearfield potentials) that significantly correlate with subjective pain ratings [6]. Furthermore, the chemo-somatosensory evoked potential (CSSEP) pain model has been successfully employed to quantify the effects of several central-acting analgesics [7]. Thus, the aim of the present study was to investigate the acute analgesic effectiveness of oral lamotrigine using the CSSEP pain model. Methods

show abstract

Lamotrigine, a new anticonvulsant: Pharmacokinetics in normal humans

Cited by 264 publications

References 7 publications

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Lack of Pharmacokinetic Interaction between Oxcarbazepine and Lamotrigine

Effects of lamotrigine on pain‐induced chemo‐somatosensory evoked potentials

Contact Info

Product

Resources

About