Population Pharmacokinetics of Valproic Acid in Adult Chinese Epileptic Patients and its Application in an Individualized Dosage Regimen

Jiao, Zheng; Wang, Changlian; Wang, Huayan; Ma, Chun-Lai; Huang, Ping-fang; Guo, Xianzhong; Liu, Yiwei

doi:10.1097/ftd.0000000000000100

Cited by 25 publications

(38 citation statements)

References 40 publications

(30 reference statements)

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“…Table summarizes the characteristics of each study. Most of the models were developed in patients with epilepsy . One study reported a model incorporating data from both epileptic and psychiatric patients .…”

Section: Resultsmentioning

confidence: 99%

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A systematic review of population pharmacokinetics of valproic acid

Methaneethorn

2018

Brit J Clinical Pharma

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Keywords nonlinear mixed effect modelling, population pharmacokinetics, systematic review, valproic acid AIMSPopulation pharmacokinetics is an essential tool that helps guide individualized dosing regimens. The aims of this systematic review are to provide knowledge concerning population pharmacokinetics of valproic acid (VPA) and to identify factors influencing VPA pharmacokinetic variability. METHODSPubMed and Embase databases were systematically searched from inception to June, 2017. Relevant articles from reference lists were also included. All population pharmacokinetic studies of VPA conducted in humans and that employed a nonlinear mixed effect modelling approach were included in this review. RESULTSTwenty-six studies were included in this review. Most studies characterized VPA pharmacokinetics as a one-compartment model. Three studies reported a two-compartment model. Body weight, dose and age were significant predictors for VPA volume of distribution (V d ). The estimated V d for one-compartment models ranged from 8.4 to 23.3 l. For two-compartment models, peripheral volumes of distribution ranged from 4.08 to 42.1 l. Frequently reported significant predictors for VPA clearance (CL VPA ) included body weight, VPA dose, concomitant medications, gender and age. The estimated CL VPA ranged from 0.206 to 1.154 l h À1 and the inter-individual variability ranged from 13.40 to 35.90%. Two studies reported population pharmacokinetics/pharmacodynamics of VPA in patients with epilepsy. Seventeen studies evaluated the performance of their final models. CONCLUSIONSSignificant predictors influencing VPA pharmacokinetics as well as model methodologies are highlighted in this review. For clinical application, CL VPA could be predicted using body weight, VPA dose, concomitant medications, gender or age. For future research, there is a knowledge gap regarding population pharmacokinetics/pharmacodynamics of VPA in a population other than epileptic patients.British Journal of Clinical Pharmacology Br J Clin Pharmacol (2018) 84 816-834 816

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Section: Resultsmentioning

confidence: 99%

“…The VPA doses of the included studies ranged from 2.4 to 87.9 mg kg À1 d À1 . Use of sustained-release formulation was reported in nine studies [21,28,31,34,37,38,[40][41][42]. Fluorescence polarization immunoassay (FPIA) and enzyme multiplied immunoassay (EMIT) were used in 57.7% and 15.4% of the studies, respectively.…”

Section: Study Characteristicsmentioning

confidence: 99%

A systematic review of population pharmacokinetics of valproic acid

Methaneethorn

2018

Brit J Clinical Pharma

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“…During backward elimination, the significance of the covariates was confirmed by removing a single covariate at a time from the full model and required an increase in the OFV of at least 6.63 (χ 2 , P <.01,df=1) to remain in the model. An additional criterion for the retention of a covariate in the model was a reduction in unexplained inter‐individual variability and improvement in the precision of the parameter estimates …”

Section: Methodsmentioning

confidence: 99%

Population pharmacokinetics analysis of intravenous busulfan in Chinese patients undergoing hematopoietic stem cell transplantation

Xie

Yang

et al. 2017

Clin Exp Pharma Physio

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There are several reports describing population pharmacokinetic (popPK) models of busulfan (BU). However, limited information is available in Chinese hematopoietic stem cell transplantation (HSCT) patients. The present study aimed to establish a popPK model of intravenous BU in Chinese HSCT patients for individualized drug therapy. The popPK model of BU was developed from a total of 284 concentration-time points from 53 patients. The effects of demographic and biochemical covariates were investigated by nonlinear mixed effect model (NONMEM) software. Plots, visual predictive check (VPC), bootstrap and normalized prediction distribution error (NPDE) were performed to determine the stability and the reliability of the final model. A one-compartment model with first-order elimination process was confirmed as the final structural model for BU. For a typical patient whose body surface area (BSA) is 1.7 m , the population typical values of CL and Vd were 11.86 L/h, and 48.2 L, respectively. The result suggested BSA showed significant influence on CL and Vd (P<.001). Plots revealed the final model was performing a goodness fit. The steady rate verified by bootstrap was 100%, relative deviation was less than 4.00%, estimated value of final model was in the 95% confidence interval (CI). The VPC results showed the observed values were almost all positioned within the 5th and 95th CIs. The mean and variance of the NPDE were 0.0363 (Wilcoxon signed-rank test, 0.298) and 0.877 (Fisher variance test, 0.134; SW test of normality, 0.108), respectively. The global adjusted P value was 0.305, which indicated that the prediction of the BU popPK model was adequate. A physician-friendly Microsoft Excel-base tool was implemented using the final popPK model for designing individualized dosing regimens.

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“…For more than 4 decades VPA stipulate in clinical practice as an anticonvulsant to control seizures in forms of tonic-clonic (grand mal), complex partial and juvenile myoclonic. Published report by International League Against Epilepsy (ILAE) authorizes the efficiency and value of ethosuximide and VPA for children with absence seizures as initial monotherapy [2][3][4][5][6][7][8][9][10][11][12]. Karlov et al [11] reported a prescription based on valproate in dose 15 -25 mg/kg/day and levetiracetam in dose 20 -25 mg/kg/day that were used in the treatment of 23 patients with juvenile myoclonic, juvenile absence, and convulsive idiopathic generalized and children absence epilepsy.…”

Section: Resultsmentioning

confidence: 99%

Review of Sodium Valproate Clinical and Biochemical Properties

Tolou-Ghamari

Palizban

2015

Zahedan J Res Med Sci

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Valproic acid is a commonly used anti-epileptic drug (AED) for prescription to control convulsion attacks. The aim of this study was to provide a review of drug management among adult epileptic population. Topic words that searched were "Valproic acid, Pharmacokinetics, Epilepsy and Iran" that search in DOAJ, Google Scholar, PubMed and Web of Science. A total of approximately 1200 articles were found and at the end, 41 articles were reviewed. With an oral dose of 10 -15 mg/kg/day in three divided doses, target blood level ranges from 50 -100 mg/L. With a half-life of 9 -16 hours, it seems that the valproic acid has a variable absorption phase. The pattern of metabolic pathways seems to be through the glucuronide conjugation and mitochondrial β-oxidation. The drug causes delay in carbamazepine elimination and may increase the amount of its metabolites. Valproic acid could decrease the clearance of amitriptyline and nortriptyline. Aspirin increase its' trough level. The doses of olanzapine suggested to be reduced when co-medicated with valproic acid. To specify the amount and effects of administrated dose an attentive pharmacotherapy-guideline seems to be useful. Due to CYP450 dependent metabolic pathways (inhibition or induction), therapeutic drug monitoring (TDM) in simultaneous prescription of valproic acid with carbamazepine, lamotrigine, phenytoin, topiramate, amitriptyline, nortriptyline, aspirin, meropenem, olanzapine and clonazepam, manifested to be necessary in clinical practice.

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Population Pharmacokinetics of Valproic Acid in Adult Chinese Epileptic Patients and its Application in an Individualized Dosage Regimen

Abstract: A PPK model was developed to estimate the individual clearance for patients taking VPA and could be applied for individualizing doses in the target population.

Cited by 25 publications

References 40 publications

A systematic review of population pharmacokinetics of valproic acid

A systematic review of population pharmacokinetics of valproic acid

Population pharmacokinetics analysis of intravenous busulfan in Chinese patients undergoing hematopoietic stem cell transplantation

Review of Sodium Valproate Clinical and Biochemical Properties

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