Population pharmacokinetics of lamotrigine in Chinese children with epilepsy.

Abstract:

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 NONMEM 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.

journal_name

Acta Pharmacol Sin

authors

He DK,Wang L,Qin J,Zhang S,Lu W,Li L,Zhang JM,Bao WQ,Song XQ,Liu HT

doi

10.1038/aps.2012.118

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

1417-23

issue

11

eissn

1671-4083

issn

1745-7254

pii

aps2012118

journal_volume

33

pub_type

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