scholarly journals Effect of CYP3A5 Genotypes on the Pharmacokinetics of Carbamazepine when used as Monotherapy or Co-Administered with Phenytoin, Phenobarbital or Valproic Acid in Thai Patients

2013 ◽  
Vol 16 (4) ◽  
pp. 502 ◽  
Author(s):  
Duangchit Panomvana ◽  
Tharathorn Traiyawong ◽  
Somchai Towanabut
Keyword(s):  
Valproic Acid ◽  
Real Time ◽  
Statistical Significance ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Single Nucleotide ◽  
Drug Concentrations ◽  
Polymerase Chain

Purpose: To determine the effects of CYP3A5 polymorphisms on carbamazepine (CBZ) pharmacokinetic parameters when CBZ is used either as monotherapy or co-administered with phenytoin (PHT), phenobarbital (PB) or valproic acid (VPA). Methods: Retrospective data were collected from an electronic database and medical records. Blood samples were obtained and drug concentrations analyzed as a part of routine therapeutic drug monitoring (TDM). Screening for wild-type CYP3A5*1 and CYP3A5*3 single nucleotide polymorphism (rs776746) by allelic discrimination assay using real-time polymerase chain reaction technique (real-time PCR) was performed. Pharmacokinetic parameters of CBZ; clearance and dose-adjusted CBZ levels in patients with different genotypes were calculated and compared. Results: Of the 70 patients assessed, 8 (11%) patients were homozygous CYP3A5*1/*1, 28 (40%) patients were heterozygous CYP3A5*1/*3, and 34 (49%) patients were homozygous CYP3A5*3/*3. The CBZ clearance and dose-adjusted CBZ levels did not significantly differ between patients with CYP3A5*1 and CYP3A5*3 alleles when CBZ was used as monotherapy. For patients who used CBZ in combination with an enzyme-inducing antiepileptic drug (AED: PHT or PB), individuals carrying the CYP3A5*1 allele (CYP3A5 expressers) showed a trend of having higher CBZ clearance and lower dose-adjusted CBZ level as compared to individuals carrying the CYP3A5*3 allele, even though no statistical significance was recorded. Nevertheless, it was observed that AEDs significantly increased CBZ clearance only in patients carrying the active CYP3A5*1 allele. Conclusions: When CBZ was used in combination with enzyme-inducing AED, CYP3A5 expressers yielded a trend toward greater susceptibility to change in CBZ clearance and showed lower dose-adjusted CBZ levels compared to CYP3A5 non-expressers. The dosage regimen should be adjusted accordingly to gain a better clinical outcome.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Immunosuppressant quantification in intravenous microdialysate – towards novel quasi-continuous therapeutic drug monitoring in transplanted patients

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Susanne Weber ◽  
Sara Tombelli ◽  
Ambra Giannetti ◽  
Cosimo Trono ◽  
Mark O’Connell ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Real Time ◽  
Drug Monitoring ◽  
Time Course ◽  
Drug Dosage ◽  
Immunosuppressive Drug ◽  
Therapeutic Drug ◽  
Continuous Sampling ◽  
Real Time Analysis ◽  
Drug Concentrations

AbstractObjectivesTherapeutic drug monitoring (TDM) plays a crucial role in personalized medicine. It helps clinicians to tailor drug dosage for optimized therapy through understanding the underlying complex pharmacokinetics and pharmacodynamics. Conventional, non-continuous TDM fails to provide real-time information, which is particularly important for the initial phase of immunosuppressant therapy, e.g., with cyclosporine (CsA) and mycophenolic acid (MPA).MethodsWe analyzed the time course over 8 h of total and free of immunosuppressive drug (CsA and MPA) concentrations measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 16 kidney transplant patients. Besides repeated blood sampling, intravenous microdialysis was used for continuous sampling. Free drug concentrations were determined from ultracentrifuged EDTA-plasma (UC) and compared with the drug concentrations in the respective microdialysate (µD). µDs were additionally analyzed for free CsA using a novel immunosensor chip integrated into a fluorescence detection platform. The potential of microdialysis coupled with an optical immunosensor for the TDM of immunosuppressants was assessed.ResultsUsing LC-MS/MS, the free concentrations of CsA (fCsA) and MPA (fMPA) were detectable and the time courses of total and free CsA comparable. fCsA and fMPA and area-under-the-curves (AUCs) in µDs correlated well with those determined in UCs (r≥0.79 and r≥0.88, respectively). Moreover, fCsA in µDs measured with the immunosensor correlated clearly with those determined by LC-MS/MS (r=0.82).ConclusionsThe new microdialysis-supported immunosensor allows real-time analysis of immunosuppressants and tailor-made dosing according to the AUC concept. It readily lends itself to future applications as minimally invasive and continuous near-patient TDM.

scholarly journals Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase 1 Influenced the Age Onset of Parkinson’s Disease

2020 ◽  
Author(s):  
Nóra Török ◽  
Rita Maszlag-Török ◽  
Kinga Molnár ◽  
Zoltán Szolnoki ◽  
Ferenc Somogyvári ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Subgroup Analysis ◽  
Snp Analysis ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Single Nucleotide ◽  
Indoleamine 2,3 Dioxygenase ◽  
Tryptophan Dioxygenase

Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) have been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

scholarly journals ADIPOQ single nucleotide polymorphisms and breast cancer in northeastern Mexican women

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ricardo M. Cerda-Flores ◽  
Karen Paola Camarillo-Cárdenas ◽  
Gabriela Gutiérrez-Orozco ◽  
Mónica Patricia Villarreal-Vela ◽  
Raquel Garza-Guajardo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Mexican Women ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Single Nucleotide ◽  
Significant Difference ◽  
Hardy Weinberg Equilibrium

Abstract Background Adiponectin gene (ADIPOQ) polymorphisms have been shown to affect adiponectin serum concentration and some have been associated with breast cancer (BC) risk. The aims of this study were to describe the frequency of single nucleotide polymorphisms (SNPs) of ADIPOQ in Mexican women with BC and to determine if they show an association with it. Methods DNA samples from 397 patients and 355 controls were tested for the ADIPOQ gene SNPs: rs2241766 (GT) and rs1501299 (GT) by TaqMan allelic discrimination assay. Hardy–Weinberg equilibrium (HWE) was tested. Multiple SNP inheritance models adjusted by age and body mass index (BMI) were examined for the SNP rs1501299. Results We found that in the frequency analysis of rs1501299 without adjusting the BMI and age, the genotype distribution had a statistically significant difference (P = 0.003). The T allele was associated with a BC risk (OR, 1.99; 95% CI 1.13–3.51, TT vs. GG; OR, 1.53; 95% CI 1.12–2.09, GT vs. GG). The SNP rs2241766 was in HW disequilibrium in controls. In conclusion, the rs1501299 polymorphism is associated with a BC risk. Conclusions Identification of the genotype of these polymorphisms in patients with BC can contribute to integrate the risk profile in both patients and their relatives as part of a comprehensive approach and increasingly more personalized medicine.

Effects of prolactin receptor genotype on the litter size of Mangalica

2011 ◽  
Vol 59 (2) ◽  
pp. 269-277 ◽  
Author(s):  
Károly Tempfli ◽  
Gergely Farkas ◽  
Zsolt Simon ◽  
Ágnes Bali Papp
Keyword(s):  
Litter Size ◽  
Fragment Length Polymorphism ◽  
Prolactin Receptor ◽  
Hair Follicles ◽  
Nucleotide Polymorphism ◽  
Allelic Discrimination ◽  
Single Nucleotide ◽  
Breed Group ◽  
Pcr Rflp ◽  
Polymerase Chain

The aim of this study was to detect different alleles of the prolactin receptor (PRLR) gene and to examine their effects on the litter size of the indigenous Hungarian pig, the Mangalica. G1789A single nucleotide polymorphism (SNP) was investigated as a candidate for litter size. Samples from 80 purebred Mangalica sows and data of their 335 litters were provided by Olmos & Tóth Ltd. Hair follicles were used to isolate the required DNA. Allelic discrimination was performed by means of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using the AluI restriction enzyme and agarose gel electrophoresis. In the population examined, the A allele was found to be preferable in the Mangalica breed group. The most advantageous AA genotype was the least prevalent (8.75%), while the frequencies of AB and BB were 40% and 51.25%, respectively. Remarkably, the average number of piglets born alive per litter was 1.11 ± 0.39 higher in sows with AA as compared to those with BB genotype. By raising the frequency of the AA genotype, the litter size is likely to increase. However, the effect of PRLR genotypes can differ among pig breeds and even lines. Further studies may be required to observe and estimate possible pleiotropic effects of this polymorphism on other traits.

Short PNA molecular beacons for real-time PCR allelic discrimination of single nucleotide polymorphisms

2004 ◽  
Vol 18 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Kenneth Petersen ◽  
Ulla Vogel ◽  
Eszter Rockenbauer ◽  
Kirsten Vang Nielsen ◽  
Steen Kølvraa ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Real Time ◽  
Real Time Pcr ◽  
Molecular Beacons ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination ◽  
Single Nucleotide

scholarly journals Optimum Use of Therapeutic Drug Monitoring and Pharmacokinetics-Pharmacodynamics in the NICU

2009 ◽  
Vol 14 (2) ◽  
pp. 66-74
Author(s):  
Peter Gal
Keyword(s):  
Drug Therapy ◽  
Therapeutic Drug Monitoring ◽  
Antiepileptic Drugs ◽  
Therapeutic Range ◽  
Drug Monitoring ◽  
Population Based ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Patient Response ◽  
Drug Concentrations

Therapeutic drug monitoring is increasingly giving way to dosing drugs based on population-based pharmacokinetic parameters, even when pharmacokinetic values vary quite a bit in individual patients. Further, drug concentrations are often considered appropriate if they are within a defined therapeutic range, even if the patient response is suboptimal. This lecture discusses the limitations of therapeutic ranges in neonates, and proposes greater emphasis on pharmacodynamic curves to individualize drug therapy. Examples are provided using methylxanthines, indomethacin, antiepileptic drugs and aminoglycosides. The potential to use pharmacokinetic findings to describe physiologic changes and occasionally assist with diagnosis is also discussed.

scholarly journals Association of HER1 and HER2 Gene Variants in the Predisposition of Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Ibrahim O. Alanazi ◽  
Jilani Purusottapatnam Shaik ◽  
Narasimha Reddy Parine ◽  
Nahla A. Azzam ◽  
Othman Alharbi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Health Concern ◽  
Nucleotide Polymorphism ◽  
Her2 Gene ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Single Nucleotide ◽  
Major Health ◽  
Risk Of Cancer ◽  
Control Study

Background. Colorectal cancer (CRC) is a major health concern worldwide. A series of sequential accumulation of genetic and epigenetic changes are responsible for the initiation and progression of diseases via the normal > adenoma > carcinoma sequence. Genetic variants in crucial cancer-causing genes are known to mediate the risk of cancer. Objective. In this case-control study, we examined single nucleotide polymorphism (SNP) in HER1 (rs763317 and rs3752651) and HER2 (rs1136201 and rs1058808) genes to assess their role in the susceptibility of CRC in a Saudi population. Methods. TaqMan allelic discrimination assay was utilized to identify the genotypes in 163 normal and 143 CRC patients. Results. In the overall analysis, the rs3752651 and rs1136201 were significantly associated with the risk of CRC. Although none of the examined SNPs had any impact on the age at which CRC was diagnosed, interestingly, three SNPs showed a significant association based on gender. The rs3752651 conferred significant protection only in men, whereas rs1136201 diminished the risk and rs1058808 considerably increased the susceptibility of CRC only in women. Conclusions. Our result suggests that these SNPs in HER1 and HER2 after validation in larger cohorts of different ethnicities may be utilized as genetic screening markers for predicting colorectal cancer predisposition.

scholarly journals Effect of sample heating on results of therapeutic drug monitoring

2021 ◽  
Vol 45 (3) ◽  
pp. 183-187
Author(s):  
Dao-Hai Cheng ◽  
Zhen-Guang Huang ◽  
Jing-Bing Zhu
Keyword(s):  
Heat Treatment ◽  
Valproic Acid ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Plasma Heating ◽  
Therapeutic Drug ◽  
Blood Concentrations ◽  
Therapeutic Drugs ◽  
Drug Concentrations

Abstract Objectives Heat treatment is a convenient measure for pathogens inactivation. The authors investigated the effects of this method on blood concentrations of six commonly therapeutic drugs. Methods Plasma and whole blood were pretreated with or without heating at 56 °C for 30 min, and drug concentrations of vancomycin, methotrexate, valproic acid, digoxin, carbamazepine, and cyclosporine were examined. Results Increased valproic acid levels after plasma heating (63.2 ± 30.2 vs. 62.1 ± 29.8 mg/L, mean recovery 102.0%) and whole blood heating (64.5 ± 30.5 vs. 62.1 ± 29.8 mg/L, mean recovery 104.6%) were observed (both p<0.05), but these differences were not considered clinically important. Recoveries of vancomycin in heat treatments varied widely, with an average and significant decrease of 15.8% in value after whole blood heating (11.7 ± 8.1 vs. 13.7 ± 8.6 mg/L, p<0.05). Conclusions Plasma or whole blood heating at 56 °C for 30 min are feasible in pathogens inactivation during monitoring methotrexate, valproic acid, digoxin, carbamazepine, and cyclosporine. However, such pretreatment seems inappropriate in monitoring vancomycin concentrations. Those results highlight the need for caution when applying heat treatment for pathogens inactivation in therapeutic drug monitoring.

scholarly journals Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase Influenced the Age Onset of Parkinson’s Disease

2021 ◽  
Author(s):  
Nóra Török ◽  
Rita Maszlag-Török ◽  
Kinga Molnár ◽  
Zoltán Szolnoki ◽  
Ferenc Somogyvári ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Subgroup Analysis ◽  
Snp Analysis ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Single Nucleotide ◽  
Indoleamine 2,3 Dioxygenase ◽  
Tryptophan Dioxygenase

Aims Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson&rsquo;s disease (PD). The first rate-limiting enzymes indoleamine 2,3- dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) has been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. Main methods SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. Key findings No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. Significance The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

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