Comparative steady state serum levels of valproic acid administered as two different formulations - Deprakine® and Orfiril®

Five healthy volunteers took part in a crossover study which examined the serum concentrations of dothiepin and northiaden after a 25 mg three times a day and a 75 mg once a day dosage regimen of Prothiaden. The inter-individual variation of serum levels was large after either schedule which is to be expected with this group of drugs. The minimum steady-state level of dothiepin tended to be lower after the single daily dose, but the differences were small and not statistically significant. The approximate maximum steady-state levels of dothiepin showed large intra- and inter-subject variation and no obvious trend. The values of the desmethylated metabolite, northiaden, tended to follow the dothiepin concentrations but were lower than the parent drug. Average steady-state levels tended, with one exception, to be very similar after both regimens with no evidence of any trend when comparing the two regimens. The study showed that the two regimens yielded similar steady-state serum concentrations both of drug and metabolite but inter-individual differences were large.

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Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti-epileptic drugs in man

Acta Neurologica Scandinavica ◽

10.1111/j.1600-0404.1980.tb01505.x ◽

2009 ◽

Vol 61 (6) ◽

pp. 357-367 ◽

Cited By ~ 32

Author(s):

Birger Stensgaard Hansen ◽

Mogens Dam ◽

Jens Brandt ◽

Eigill F. Hvidberg ◽

Helle Angelo ◽

...

Keyword(s):

Steady State ◽

Protein Binding ◽

Serum Levels ◽

Steady State Serum

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Effect of Genetic Polymorphisms of CYP2C19 on the Steady-state Serum Concentrations of Valproic Acid in Chinese Han Patients With Schizophrenia

10.21203/rs.3.rs-38955/v1 ◽

2020 ◽

Author(s):

Shengdong WANG ◽

Jing Li ◽

Mingfen Song ◽

Pan Yan ◽

Xuan Ju ◽

...

Keyword(s):

Valproic Acid ◽

Steady State ◽

Genetic Polymorphisms ◽

Fixed Dose ◽

Serum Concentrations ◽

Chinese Han ◽

Chromatography Method ◽

Steady State Serum ◽

The Mean ◽

Mean Concentration

Abstract Valproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproic acid augmentation therapy in schizophrenia. Interindividual variability in valproic acid dose and serum concentration may reflect functional consequences of genetic polymorphisms in genes encoding drug-metabolizing enzymes. The aim of this study was to determine the relationship between serum concentrations of valproic acid and single nucleotide polymorphisms of the cytochrome P450 (CYP) 2C19 gene in patients with schizophrenia. All patients had been receiving fixed dose of valproic acid for at least 2 weeks. The daily doses were 0.5–1.5 g. No other drugs except olanzapine were coadministered. Serum concentrations of valproic acid were measured using the ultra-high performance liquid chromatography method with mass-spectrometric detection. The CYP2C19 (CYP2C19*2 G681A and CYP2C19*3 G636A) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid was significantly higher in patients with 1 (P = 0.029) or 2 (P = 0.007) mutated alleles for CYP2C19 than in those without mutated alleles. The mean concentration/dose ratios of valproic acid was significantly higher in patients with CYP2C19 *1/*2 genotype (P = 0.029) or CYP2C19 *2/*3 genotype (P = 0.014) than in those with CYP2C12 *1/*1 genotype. The findings of this study suggest that CYP2C19 genotypes play an important role in controlling steady-state serum concentrations of valproic acid in Chinese Han population.

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