Population Pharmacokinetics of Lamotrigine

Chan, Vivien; Morris, Raymond G.; Ilett, Kenneth F.; Tett, S. E.

doi:10.1097/00007691-200112000-00006

Cited by 52 publications

(49 citation statements)

References 24 publications

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“…This unexplained variability was of similar magnitude to those reported in earlier studies [7,[13][14][15][16][32][33][34] .…”

Section: Discussionsupporting

confidence: 88%

“…Despite LTG's wide clinical use, standard npg dosage regimens continue to be used even though they may often be suboptimal because of the high variability found in CL values in the target population [7,10,[13][14][15][16][17][18] . This observation, together with previous studies that have established definable relationships between LTG blood concentrations and therapeutic and toxic effects [19][20][21] , justify TDM as an indicator of drug exposure for the individualization of LTG doses [4][5] .…”

Section: Discussionmentioning

confidence: 99%

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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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“…This unexplained variability was of similar magnitude to those reported in earlier studies [7,[13][14][15][16][32][33][34] .…”

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Wang

Qin

et al. 2012

Acta Pharmacol Sin

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“…This competition may prolong lamotrigine's half-life to 60 h. Sertaline may also result in similar lamotrigine intoxication. The T½ is 8-20 h in the presence of concomitant enzyme inducers [22]. With severe hepatic dysfunction the T½ may be increased to a median of 110 h and in the case of severe renal dysfunction to 50 h [23].…”

Section: Which Drugs and Conditions When Added To Lamotrigine Can Incmentioning

confidence: 99%

Case Files of the University of California San Francisco Medical Toxicology Fellowship: Lamotrigine Toxicity

Fleurat

Smollin

2012

J. Med. Toxicol.

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A 56-year-old man was brought to the emergency department (ED) after he was found seizing on the floor by his family. His brother described hearing a thump in his room and witnessed him having a full body clonic seizure that lasted approximately 2 min. When emergency medical service arrived, he was found on the floor with altered mental status and with signs of facial trauma. No medications were administered en route to the hospital.On arrival to the ED, he was initially confused and mumbling incoherently. He was noted to be only oriented to self, and would not reliably follow commands. Approximately 1 h after arrival, he became agitated, seemed more confused, and would not follow any commands. Initial vital signs were: blood pressure, 147/76 mmHg; pulse, 81/min; respiratory rate, 18/min; temperature, 35°C by tympanic measurement; and oxygen saturation was 100% on room air. On physical exam, his pupils were 4 mm and reactive bilaterally. Extraocular movements appeared intact by observation only and there was no nystagmus. He had a nasal deformity and laceration to the right side of his tongue. The chest exam was normal with the exception of a large median sternotomy scar. His abdomen was soft, nontender, and there were no signs of bladder distension. Bowel sounds were noted to be present. There was no evidence of bowel or bladder incontinence. The neurological exam was notable for decreased attention, inability to follow commands, inability to repeat examiner's phrases, and markedly reduced language skills. The patient had spastic muscle tone with resistance to motion both with flexion and extension of all extremities. Deep tendon reflexes were noted to be 2+ in bilateral upper extremities and 3+ in bilateral lower extremities without clonus.

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“…LTG is metabolized by uridine diphosphate glucuronosyltransferase (UGT), forming mainly an inactive 2-N-glucuronide (2-N-GLUC) by isoenzyme UGT1A4 [1]. Dose/plasma concentration ratios have been reported to be lower in adults than in children [2], but early studies of population pharmacokinetics in adults have failed to find an influence of age and gender on LTG clearance [3][4][5]. This may to some extent depend on the small numbers of patients in different age groups.…”

Section: Introductionmentioning

confidence: 99%