Drug Metabolizing Enzyme and Transporter Genes Associated with Plasma Risperidone Level in Thai Autism Spectrum Disorder

2017 ◽  
Vol 41 (S1) ◽  
pp. s304-s305
Author(s):  
C. Sukasem
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Genetic Variants ◽  
Plasma Concentrations ◽  
Autism Spectrum ◽  
Metabolic Ratio ◽  
Transporter Family ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
State Plasma

BackgroundThe associations between genetic variants of drug metabolizing enzyme and transporter (DMET) genes and steady-state plasma concentrations of risperidone, 9-hydroxyrisperidone, total active-moiety, and metabolic ratio remain unclear.ObjectiveThe objective of the present study was to present the results of the association between genetic variants of DMET gene and steady-state plasma concentration risperidone and its metabolite using Affymetrix DMET Plus genotyping microarray.MethodsSubjects eligible for this study included male and female adolescents with ASD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and being treated with risperidone for at least 4 weeks prior to the blood sample collection. Blood samples were drawn prior to the next dose of risperidone intake to determine the steady-state plasma trough concentrations of risperidone and 9-hydroxyrisperidone. Genotyping profile was obtained using the microarray. Steady-state plasma risperidone and 9-hydroxyrisperidone were measured using liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay.ResultsThe polymorphisms of UGT2B4, CYP2D6 were highly associated with metabolic ratio. Of all the DMET analysis, ABCB11 (3084A > G, 420A > G, 368G > A, and 236G > A) and ADH7 (690G > A and –5360G > A) were found to be associated with plasma concentrations of risperidone (P < 0.01). In addition, 6 genetic variations among the SLC transporter family were associated with the plasma concentration of 9-hydroxyrisperidone.DiscussionsThis study provides a pharmacogenomic approach to investigate further among the DMET genetic variants which influence plasma concentration of risperidone. The treatment of ASD should be based on genetic factors making the challenge of psychopharmacological treatment more efficacious with lesser adverse events.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

scholarly journals Association Between Genetic Polymorphisms and Steady-State Plasma Concentration of Warfarin Optical Isomers

2020 ◽  
Author(s):  
Yiwei Liu ◽  
Quanyao Chen ◽  
Wai-Kit Ming ◽  
Feiyu Wang ◽  
Rongfang Lin ◽  
...  
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Ultra Performance Liquid Chromatography ◽  
Optical Isomers ◽  
Chi Square ◽  
Genotype Frequencies ◽  
Significant Difference ◽  
Chi Square Analysis ◽  
State Plasma

Abstract Background We evaluated the effects of CYP2C19*2, CYP2C9*3, VKORC1 A1639G, CYP4F2, and MDR1 C3435T gene polymorphisms on the plasma concentrations of R- and S-warfarin enantiomers at the same dose.Methods The plasma concentrations of R- and S-warfarin were determined by ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) in 136 patients. The PCR-RFLP genotyping results were verified by pyrosequencing. The Hardy–Weinberg equilibrium of genotype frequencies was assessed using the Chi-square analysis. Relationships between genotype and plasma concentrations of the enantiomers were analyzed by Kruskal–Wallis test.Results There was no significant difference in the dosage between groups (P > 0.05). The CYP2C19*2, CYP2C9*3, CYP4F2, MDR1 C3435T, and VKORC1 A1639G mutation frequencies were 37.5%, 6.25%, 19.12%, 31.25%, and 3.31%, respectively. The plasma concentrations were non-normally distributed. The S-warfarin plasma concentration was significantly higher in CYP2C9*3 carriers than in non-carriers (P = 0.018) and in patients carrying the T allele of CYP4F2 than those carrying the C allele (P = 0.03). The VKORC1 A1639G polymorphism did not affect the steady-state plasma concentrations of R- and S-warfarin. The enantiomer ratio in homozygous patients (GG) was significantly lower than that in heterozygous patients (GA) and those lacking the mutation (AA) (P = 0.039). Enantiomer plasma levels were not significantly different between MDR1 C3435T and CYP2C19*2 (P > 0.052).Conclusions The CYP2C9*3 and CYP4F2 mutations are associated with increased plasma concentrations of S-warfarin. The VKORC1 A1639G polymorphism might affect the plasma ratio of R- and S-warfarin. Maintenance dose reduction during warfarin administration can be considered for patients with the CYP2C9*3 and CYP4F2 mutations.

Monitoring plasma concentrations of psychotropic drugs

1974 ◽  
Vol 12 (2) ◽  
pp. 6-8
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Tissue Concentration ◽  
Plasma Concentrations ◽  
Water Concentration ◽  
Plasma Samples ◽  
Active Metabolites ◽  
The Relationship ◽  
The Brain ◽  
Reliable Methods

Techniques are now available for estimating the plasma concentration of several drugs used in psychiatry. These techniques are clearly important for research but they can hardly be expected to improve the clinical management of patients unless the estimation is sensitive, reliable and reasonably quick; the method should be specific for the particular drug but should also specifically estimate any active metabolites. Even when reliable figures have been obtained, much more information is needed before they can be interpreted. The relationship between plasma (or plasma water) concentration and relevant tissue concentration (e. g. in the brain) must be known. Plasma samples should be taken at appropriate times, e. g. after the attainment of ‘steady-state’ conditions: plasma and tissue levels will then be in equilibrium. Diagnoses must be soundly based if inferences are to be drawn. Reliable methods of assessing clinical response must be available. These requirements pose difficult problems in psychiatry.

scholarly journals Fasting Remnant Lipoprotein Cholesterol and Triglyceride Concentrations Are Elevated in Nondiabetic, Insulin-Resistant, Female Volunteers1

1999 ◽  
Vol 84 (11) ◽  
pp. 3903-3906 ◽  
Author(s):  
Fahim Abbasi ◽  
Tracey McLaughlin ◽  
Cindy Lamendola ◽  
Helen Yeni-Komshian ◽  
Akira Tanaka ◽  
...  
Keyword(s):  
Steady State ◽  
Plasma Concentrations ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Insulin Resistant ◽  
Remnant Lipoprotein ◽  
Increased Risk ◽  
Resistant Group ◽  
State Plasma

This study was initiated to test the hypothesis that plasma concentrations of remnant lipoproteins would be higher after an overnight fast in insulin-resistant compared to insulin-sensitive volunteers. Forty-three healthy nonobese women were studied, divided into insulin-resistant (n = 21) and insulin-sensitive (n = 22) groups on the basis of their steady state plasma glucose (SSPG) concentration at the end of a 180-min infusion of octreotide acetate, insulin, and glucose. Under these conditions, steady state plasma insulin concentrations are similar in all subjects (∼60μ U/mL), and the higher the SSPG concentrations, the more insulin resistant the individual. By selection, mean (±sem) SSPG concentrations were significantly higher (P &lt; 0.001) in the insulin-resistant group (210 ± 7 vs. 78 ± 3 mg/dL). In addition, the insulin-resistant group had higher triglycerides (198 ± 27 vs. 101 ± 12 mg/dL; P &lt; 0.005) and lower high density lipoprotein cholesterol (48 ± 4 vs. 60 ± 4 mg/dL; P &lt; 0.05) concentrations. Finally, insulin resistance was associated with higher remnant lipoprotein particle concentrations of cholesterol (7.2 ± 0.8 vs. 4.4 ± 0.3; P &lt; 0.005) and triglycerides (22.2 ± 3.4 vs. 8.5 ± 1.0; P &lt; 0.001). All of these differences were seen despite the fact that the two groups were similar in terms of age and body mass index. These results identify additional abnormalities in lipoprotein metabolism that may contribute to the increased risk of coronary heart disease seen in insulin-resistant, nondiabetic subjects (syndrome X).

scholarly journals The Role of Pharmacokinetics in Anaesthesia: Application to Intravenous Infusions

1987 ◽  
Vol 15 (1) ◽  
pp. 7-14 ◽  
Author(s):  
D. R. Stanski
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Drug Dose ◽  
Metabolic Clearance ◽  
Drug Infusion ◽  
Fixed Rate ◽  
Elimination Half

Pharmacokinetic concepts describe the relationship between drug dose and resulting plasma concentration. A drug's pharmacokinetic profile can be described by distribution and elimination half-lives, initial volume of distribution, steady-state distribution volume, and metabolic and distributional clearance. After initiating a fixed rate of drug infusion, four to five terminal elimination half-lives are required to reach a steady state of constant plasma concentration. If a loading dose is given, a steady state can be achieved more rapidly. The most rapid method of achieving a constant plasma concentration involves using a variable rate of drug infusion that adjusts for the metabolic clearance and distribution of the drug. Computer-driven infusion pumps can be used to rapidly achieve, then maintain, constant plasma concentrations of a drug.

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