Urinary Metabolites of Valproic Acid in Epileptic Patients.

Katayama, Hirokazu; Watanabe, Miki; Yoshitomi, Hironori; Yoshida, Hisahiro; Kimoto, Hiroo; Kamiya, Akira; Hayashi, Takashi; Akimura, Tatsuo

doi:10.1248/bpb.21.304

Cited by 19 publications

(5 citation statements)

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“…Different biological matrices have been examined, including plasma [240][241][242][243], serum [244], urine [245] and tears [246]. Derivatization is required in order to make VPA accessible to GC-analysis.…”

Section: Methods Of Analysismentioning

confidence: 99%

Antipsychotic and Antiepileptic Drugs in Bipolar Disorder: The Importance of Therapeutic Drug Monitoring

Musenga

Saracino

Sani³

et al. 2009

CMC

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Bipolar disorder (BD) is a long-term illness with mood swings which are characterized by recurrent episodes of mania/hypomania and depression, with variable interpolations of relatively asymptomatic periods, called euthymic, in which, however, some psychopathological symptoms may persist. Although mood stabilizers, such as lithium, are the first-line treatment for the prevention of new BD episodes, combination therapy has become the standard of care for BD patients. Besides lithium, the use of a mood stabilizer along with an atypical antipsychotic is recommended in many patients. Recently, atypical antipsychotics (quetiapine, olanzapine, risperidone and aripiprazole) and antiepileptic agents (valproate, lamotrigine and oxcarbazepine) are increasingly used as mood stabilizers. To reduce side effects and optimize treatment it is important to perform accurate monitoring of drug blood levels in these patients, who are often treated with multiple drugs. Therapeutic drug monitoring (TDM) is in fact a powerful tool that, starting from clinical-chemical correlation data, allows to tailor-cut treatment to the specific needs of individual patients; hence the need to have reliable analytical methods available for the determination of plasma levels of drugs and their metabolites. Analyses of biological samples are mainly carried out using high-performance liquid chromatography (HPLC) coupled with different detectors, capillary electrophoresis and gas-chromatography. Various procedures are employed to remove biological interferences before analyzing the samples. This review focuses on currently available analytical TDM methods for atypical antipsychotics and antiepileptic agents used in the treatment of patients with bipolar disorder. Advantages and limitations of the various analytical methods will be reviewed and discussed, together with an evaluation of the role of TDM.

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Section: Methods Of Analysismentioning

confidence: 99%

Antipsychotic and Antiepileptic Drugs in Bipolar Disorder: The Importance of Therapeutic Drug Monitoring

Musenga

Saracino

Sani³

et al. 2009

CMC

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“…The final reaction of the b-oxidation cycle of straight-chain fatty acids consists of the thiolytic cleavage of 3-ketoacyl-CoA derivatives, a reaction catalysed by the 3-ketoacyl-CoA thiolases producing a chainshortened acyl-CoA and acetyl-CoA. 3-ketoVPA is the major mitochondrial metabolite excreted in vivo (Battino et al 1995;Katayama et al 1998), and the measurement of the combined excretion of D 2 -VPA and 3-ketoVPA correlates with the b-oxidation of VPA in vivo . Because of the efficient excretion of 3-keto-VPA, produced by hydrolysis of 3-ketovalproyl-CoA, the cleavage of 3-ketovalproyl-CoA was considered nonexistent.…”

Section: Activation Of Vpa To Valproyl-coa and Sites Of Activationmentioning

confidence: 99%

Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: A review

Silva

Aires

Luis

et al. 2008

J of Inher Metab Disea

332

268

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Valproic acid (VPA; 2-n-propylpentanoic acid) is widely used as a major drug in the treatment of epilepsy and in the control of several types of seizures. Being a simple fatty acid, VPA is a substrate for the fatty acid beta-oxidation (FAO) pathway, which takes place primarily in mitochondria. The toxicity of valproate has long been considered to be due primarily to its interference with mitochondrial beta-oxidation. The metabolism of the drug, its effects on enzymes of FAO and their cofactors such as CoA and/or carnitine will be reviewed. The cumulative consequences of VPA therapy in inborn errors of metabolism (IEMs) and the importance of recognizing an underlying IEM in cases of VPA-induced steatosis and acute liver toxicity are two different concepts that will be emphasized.

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“…Regarding the renal profile, patient 2 showed an increase in glycine level in urine (tested one time, only). Such increase may be due to valproic acid (VA) since it has been typically associated with hyperglycinuria [ 35 , 36 ]. The MRIs of patients 1 and 2 were almost identical as they showed significant generalized atrophy in the cerebellar hemispheres, corpus callosum, and brain stem.…”

Section: Discussionmentioning

confidence: 99%

A Novel GEMIN4 Variant in a Consanguineous Family Leads to Neurodevelopmental Impairment with Severe Microcephaly, Spastic Quadriplegia, Epilepsy, and Cataracts

Hesham

Al-Bakheet

AlRuways

et al. 2021

Genes

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Pathogenic variants in GEMIN4 contribute to a hereditary disorder characterized by neurodevelopmental features, microcephaly, cataracts, and renal abnormalities (known as NEDMCR). To date, only two homoallelic variations have been linked to the disease. Moreover, clinical features associated with the variants have not been fully elucidated yet. Here, we identified a novel variant in GEMIN4 (NM_015721:exon2:c.440A>G:p.His147Arg) in two siblings from a consanguineous Saudi family by using whole exome sequencing followed by Sanger sequence verification. We comprehensively investigated the patients’ clinical features, including brain imaging and electroencephalogram findings, and compared their phenotypic characteristics with those of previously reported cases. In silico prediction and structural modeling support that the p.His147Arg variant is pathogenic.

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Urinary Metabolites of Valproic Acid in Epileptic Patients.

Cited by 19 publications

References 0 publications

Antipsychotic and Antiepileptic Drugs in Bipolar Disorder: The Importance of Therapeutic Drug Monitoring

Antipsychotic and Antiepileptic Drugs in Bipolar Disorder: The Importance of Therapeutic Drug Monitoring

Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: A review

A Novel GEMIN4 Variant in a Consanguineous Family Leads to Neurodevelopmental Impairment with Severe Microcephaly, Spastic Quadriplegia, Epilepsy, and Cataracts

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