Predictors of valproic acid steady-state serum levels in adult and pediatric psychiatric inpatients: a comparative analysis

被引：0

作者：

Avrahami, Matan ^{[1
]}

Liwinski, Timur ^{[2
]}

Eckstein, Zafrir ^{[3
]}

Peskin, Miriam ^{[1
]}

Perlman, Polina ^{[1
]}

Sarlon, Jan ^{[2
]}

Lang, Undine E. ^{[2
]}

Amital, Daniela ^{[4
]}

Weizman, Abraham ^{[1
,5
,6
]}

机构：

[1] Tel Aviv Univ, Petah Tikva & Fac Med, Geha Mental Hlth Ctr, Young Children Dept,Child & Adolescent Div, Tel Aviv, Israel

[2] Univ Basel, Univ Psychiat Clin Basel, Clin Adults, Wilhelm Klein Str 27, CH-4002 Basel, Switzerland

[3] Bengurion Univ Negev, Fac Hlth Sci, Geha Mental Hlth Ctr, Petah Tikva & Sch Pharm, Beer Sheva, Israel

[4] Bengurion Univ Negev, Barzilai Med Ctr, Div Psychiat, Ashqelon, Israel

[5] Felsenstein Med Res Ctr, Lab Biol & Mol Psychiat, Petah Tiqwa, Israel

[6] Tel Aviv Univ, Sagol Sch Neurosci, Tel Aviv, Israel

来源：

PSYCHOPHARMACOLOGY | 2024年 / 241卷 / 09期

关键词：

Valproic acid; Therapeutic drug-monitoring; Predictors; Pharmacokinetics; Mood stabilizer; Polypharmacy; Co-medication; Precision psychiatry; POPULATION PHARMACOKINETIC MODEL; PROTEIN-BINDING; CLINICAL PHARMACOKINETICS; BIPOLAR DISORDER; CHILDREN; DIAZEPAM; POLYPHARMACY; ANTICONVULSANT; RISPERIDONE; EPILEPSY;

D O I：

10.1007/s00213-024-06603-y

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Rationale: Valproic acid (VPA) is commonly used as a second-line mood stabilizer or augmentative agent in severe mental illnesses. However, population pharmacokinetic studies specific to psychiatric populations are limited, and clinical predictors for the precision application of VPA remain undefined. Objectives To identify steady-state serum VPA level predictors in pediatric/adolescent and adult psychiatric inpatients. Methods We analyzed data from 634 patients and 1,068 steady-state therapeutic drug monitoring (TDM) data points recorded from 2015 to 2021. Steady-state VPA levels were obtained after tapering during each hospitalization episode. Electronic patient records were screened for routine clinical parameters and co-medication. Generalized additive mixed models were employed to identify independent predictors. Results Most TDM episodes involved patients with psychotic disorders, including schizophrenia (29.2%) and schizoaffective disorder (17.3%). Polypharmacy was common, with the most frequent combinations being VPA + quetiapine and VPA + promethazine. Age was significantly associated with VPA levels, with pediatric/adolescent patients (< 18 years) demonstrating higher dose-adjusted serum levels of VPA (beta = 7.6 +/- 2.34, p < 0.001) after accounting for BMI. Women tended to have higher adjusted VPA serum levels than men (beta = 5.08 +/- 1.62, p < 0.001). The formulation of VPA (Immediate-release vs. extended-release) showed no association with VPA levels. Co-administration of diazepam exhibited a dose-dependent decrease in VPA levels (F = 15.7, p < 0.001), suggesting a potential pharmacokinetic interaction. Conclusions This study highlights the utility of population-specific pharmacokinetic data for VPA in psychiatric populations. Age, gender, and co-administration of diazepam were identified as predictors of VPA levels. Further research is warranted to establish additional predictors and optimize the precision application of VPA in psychiatric patients.

引用

页码：1883 / 1894

页数：12

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