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

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.

scholarly journals Effect of CYP2C19 polymorphisms on serum valproic level acid in Chinese Han patients with schizophrenia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
S. Wang ◽  
J. Li ◽  
M. Song ◽  
P. Yan ◽  
X. Ju ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Genetic Polymorphisms ◽  
Statistical Power ◽  
Fixed Dose ◽  
Type I ◽  
Serum Concentrations ◽  
Chinese Han ◽  
Acid Therapy ◽  
The Mean ◽  
Mean Concentration

AbstractValproic 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 rs4244285 and CYP2C19*3 G636A rs4986893) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid were significantly higher in patients with CYP2C19 *1/*2 genotype (P < 0.01) or CYP2C19 *2/*3 genotype (P < 0.01) than in those with CYP2C12 *1/*1 genotype. The mean concentration/dose ratios of valproic acid were significantly higher in patients with 1 (P < 0.01) or 2 (P < 0.01) mutated alleles for CYP2C19 than in those without mutated alleles. And the post hoc analysis revealed that the result has acceptable statistical (power (1 – β) = 0.8486 at type I  level of 0.05) to support the observed significant associations for CYP2C19 SNPs and serum C/D ratios of valproic acid. The findings of this study suggest that the genetic polymorphisms of CYP2C19 significantly affect the steady-state serum concentrations of valproic acid in Chinese Han population. The determination of the CYP2C19 genotypes may be useful for dosing adjustment in schizophrenia patients on valproic acid therapy.

scholarly journals Circulating concentrations of insulin like growth factor-1 in female dogs with spontane-ous mammary tumours

2018 ◽  
Vol 74 (1) ◽  
pp. 6054-2018
Author(s):  
MAREK SZCZUBIAŁ ◽  
ROMAN DABROWSKI ◽  
WOJCIECH ŁOPUSZYŃSKI ◽  
MARIOLA BOCHNIARZ ◽  
MAGDALENA KRAWCZYK ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Cell Differentiation ◽  
Growth Factor ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
Elisa Kit ◽  
Mammary Tumours ◽  
The Mean ◽  
Grade 3 ◽  
Mean Concentration

The aim of this study was the investigation of the circulating concentration of IGF-1 in female dogs with spontaneous mammary tumours. The study was performed on 34 female dogs undergoing surgery due to spontaneously occurring mammary gland tumours (24 malignant and 10 benign) and 10 clinically healthy fe-male dogs. The serum concentrations of IGF-1 were determined by specific ELISA Kit assay. The mean con-centrations of IGF-1 were significantly higher (P < 0.05) both in dogs with malignant (173.35 ± 120.45 ng/ml) and benign (130.58 ± 59.0 ng/ml) mammary tumours than in healthy controls (117.45±71.0 ng/ml). In the group of female dogs with mammary carcinomas, the mean concentration of IGF-1 gradually increased from 132.85 ± 65.64 ng/ml in dogs with grade 1 tumours to 317.74 ± 119.25 ng/ml in those with grade 3 tumours, and significant differences (P < 0.05) were found among dogs with various grade tumours. These findings suggest that circulating IGF-1 may play an important role in the pathogenesis of canine mammary tumour. Moreover, high IGF-1 levels may reflect tumour cell differentiation into a more aggressive phenotype. .

Relationship of steady-state serum concentrations of amiodarone and desethylamiodarone to therapeutic efficacy and adverse effects

1987 ◽  
Vol 82 (6) ◽  
pp. 1102-1108 ◽  
Author(s):  
Ruth Falik ◽  
Belinda T. Flores ◽  
Leslie Shaw ◽  
Gene A. Gibson ◽  
Mark E. Josephson ◽  
...  
Keyword(s):  
Steady State ◽  
Adverse Effects ◽  
Therapeutic Efficacy ◽  
Serum Concentrations ◽  
Steady State Serum ◽  
Relationship Of

Carbamazepine-Isoniazid Interaction

PEDIATRICS ◽  
1983 ◽  
Vol 71 (1) ◽  
pp. 139-139
Author(s):  
J. M. WRIGHT
Keyword(s):  
Case Report ◽  
Steady State ◽  
Significant Interaction ◽  
Similar Case ◽  
Drug Regimen ◽  
Acetylator Phenotype ◽  
Serum Concentrations ◽  
Slow Acetylator ◽  
Steady State Serum ◽  
Clinically Significant

To the Editor.— The case report of carbamazepine intoxication secondary to isoniazid administration recently described in this journal1 is a clinically significant interaction. I have previously presented2 a similar case in which a patient receiving carbamazepine, valproate, and nitrazepam developed severe carbamazepine intoxication when isoniazid was added to the drug regimen. The patient was determined to have inherited the slow acetylator phenotype. On careful rechallenge, 300 mg of isoniazid increased carbamazepine steady-state serum concentrations by 85% and decreased carbamazepine clearance by 45%.

Subchronic Toxicity of S-111-S-WB in Sprague Dawley Rats

2010 ◽  
Vol 29 (4) ◽  
pp. 358-371 ◽  
Author(s):  
Jozef J. W. M. Mertens ◽  
Daniel W. Sved ◽  
Gary B. Marit ◽  
Nichole R. Myers ◽  
Phil L. Stetson ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Steady State ◽  
Ammonium Salts ◽  
Serum Concentrations ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
Lower Serum ◽  
Sprague Dawley Rats ◽  
Steady State Serum ◽  
Effect Level

S-111-S-WB, a mixture of perfluoro fatty acid ammonium salts (C6-C13), was administered orally to Crl:CD (SD)IGS-BR rats. Higher hepatic β-oxidation and liver weights with hepatocellular hypertrophy were present at the 0.125 and 0.6 mg/kg/d dosage. The 0.6 mg/kg/d males developed hepatocellular degeneration and necrosis. Lower serum protein and higher bilirubin and BUN were seen in the 0.6 mg/kg/d males and lower globulin and higher alkaline phosphatase in the 0.125 mg/kg/d males and 0.6 mg/kg/d animals. After 2 weeks, serum concentrations of pentadecafluorooctanoic acid (C8), heptadecafluorononanoic acid (C9), perfluoroundecanoic acid (C11), and perfluorotridecanoic acid (C13) were constant for at least 8 hours. After 90 days, only C9 in the 0.025 mg/kg/d females had reached steady state. Serum C8 and C9 concentrations in the males were 10-fold higher than in the females, whereas C11 and C13 were similar for both genders. The main elimination was via the urine for C8 (males) and C9 (females), and via the feces for C11 and C13. The no-observed-effect level (NOEL) was 0.025 mg/kg/d for the males and 0.125 mg/kg/d for the females.

Ticarcillin: Pharmacokinetics in Man According to Different Administration Schedules

1977 ◽  
Vol 5 (5) ◽  
pp. 308-312 ◽  
Author(s):  
A Dalhoff ◽  
D Höffler
Keyword(s):  
Steady State ◽  
Total Dose ◽  
Continuous Infusion ◽  
Intravenous Infusion ◽  
Half Life ◽  
Loading Dose ◽  
Serum Concentrations ◽  
Semisynthetic Penicillin ◽  
Steady State Serum ◽  
Administration Schedules

The pharmacokinetic characteristics of ticarcillin, a semisynthetic penicillin more active than carbenicillin against Pseudomonas, were studied. Following a rapid intravenous infusion of 1 g, 2 g, 5 g and 10 g ticarcillin respectively the serum half-life was 72·4 minutes independent of the dosage administered. If ticarcillin is administered under steady-state conditions, e.g. continuous infusion of either 2 g/hr or 1 g/hr following a loading dose of 1 g (total dose 5 g) the average steady-state serum concentrations are 125 μg/ml and 105 μg/ml respectively.

scholarly journals Steady state serum concentrations of pravastatin and digoxin when given in combination.

1993 ◽  
Vol 36 (3) ◽  
pp. 263-265 ◽  
Author(s):  
J Triscari ◽  
BN Swanson ◽  
DA Willard ◽  
AI Cohen ◽  
A Devault ◽  
...  
Keyword(s):  
Steady State ◽  
Serum Concentrations ◽  
Steady State Serum
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