scholarly journals Palpitations and Asthenia Associated with Venlafaxine in a CYP2D6 Poor Metabolizer and CYP2C19 Intermediate Metabolizer

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Sofia Garcia ◽  
Michael Schuh ◽  
Anvir Cheema ◽  
Herjot Atwal ◽  
Paldeep S. Atwal
Keyword(s):  
Active Metabolite ◽  
Extended Release ◽  
Pharmacokinetic Parameters ◽  
Poor Metabolizer ◽  
Patient Case ◽  
The Common ◽  
Altered Pharmacokinetic ◽  
A Minor ◽  
Intermediate Metabolizer ◽  
Minor Extent

Cardiotoxicity has been extensively reported in venlafaxine (VEN) overdoses. Asthenia is also among the common side effects described for this antidepressant. VEN is metabolized mainly by CYP2D6 and to a minor extent by CYP2C19 to the major active metabolite O-desmethylvenlafaxine (ODV). Altered pharmacokinetic parameters in patients with polymorphisms in the CYP2D6 and CYP2C19 genes that result in decreased enzymatic activity have been documented. Here we describe a patient case of VEN associated palpitations and asthenia. The patient takes VEN extended release 150 mg twice daily. Genotyping confirmed the patient is a poor metabolizer for CYP2D6 and an intermediate metabolizer for CYP2C19. We propose that the palpitations and asthenia are related to sustained VEN exposure due to reduced metabolism.

Liquid Chromatography-Tandem Mass Spectrometry Method for Ticagrelor and its Active Metabolite Determination in Human Plasma: Application to a Pharmacokinetic Study

2020 ◽  
Vol 16 (5) ◽  
pp. 602-608
Author(s):  
Niloufar Marsousi ◽  
Serge Rudaz ◽  
Jules A. Desmeules ◽  
Youssef Daali
Keyword(s):  
Clinical Trial ◽  
Formic Acid ◽  
Human Plasma ◽  
Active Metabolite ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Healthy Male ◽  
Coronary Syndrome ◽  
Healthy Male Volunteers ◽  
Male Volunteers

Background: Ticagrelor is a highly recommended new antiplatelet agent for the treatment of patients with acute coronary syndrome at moderate or high ischemic risk. There is a real need for rapid and accurate analytical methods for ticagrelor determination in biological fluids for pharmacokinetic studies. In this study, a sensitive and specific LC-MS method was developed and validated for quantification of ticagrelor and its Active Metabolite (AM) in human plasma over expected clinical concentrations. Methods: Samples were handled by Liquid-Liquid Extraction (LLE). A linear gradient was applied with a mobile phase composed of formic acid 0.1% and acetonitrile with 0.1% of formic acid using a C18 reversed-phase column. MS spectra were obtained by electrospray ionization in negative mode and optimized at 521.4→360.9 m/z, 477.2→361.2 m/z and 528.1→367.9 m/z transitions for ticagrelor, AM and ticagrelor-d7, respectively. Results: This method allowed rapid elution, in less than 4 minutes, and quantification of concentrations as low as 2 ng/mL for ticagrelor and 1 ng/mL for AM using only 100 μL of human plasma. LLE using hexane/ethyl acetate (50/50) was an optimal compromise in terms of extraction recovery and endogenous compounds interference. Trueness values of 87.8% and 89.5% and precisions of 84.1% and 93.8% were obtained for ticagrelor and AM, respectively. Finally, the usefulness of the method was assessed in a clinical trial where a single 180 mg ticagrelor was orally administered to healthy male volunteers. Pharmacokinetic parameters of ticagrelor and its active metabolite were successfully determined. Conclusion: A sensitive and specific quantification LC-MS-MS method was developed and validated for ticagrelor and its active metabolite determination in human plasma. The method was successfully applied to a clinical trial where a single ticagrelor 180 mg dose was orally administered to healthy male volunteers. The described method allows quantification of concentrations as low as 2 ng/mL of ticagrelor and 1 ng/mL of the metabolite using only 100 μL of plasma.

Gene Frequency of CYP2D6*4 and *10 Variants in Karachi Population

2020 ◽  
Vol 17 ◽  
Author(s):  
Tamkeen Fatima ◽  
Farah Zeb ◽  
A. Dar Farooq
Keyword(s):  
Antipsychotic Drugs ◽  
Screening Program ◽  
Restriction Enzymes ◽  
Normal Subjects ◽  
Control Group ◽  
Poor Metabolizer ◽  
Cyp2d6 Polymorphism ◽  
Wild Allele ◽  
Schizophrenic Patients ◽  
Intermediate Metabolizer

Background: CYP2D6 is to be considered the most pronounced gene in pharmacegenetic field which is involved in metabolizing ~25% of all clinically used neuroleptic drugs and other antidepressants. We designed a study to evaluate differential expression of CYP2D6*4 and CYP2D6*10 variants which are very prevalent in Asian countries and exhibit variation in drug metabolizing ability that affect therapeutic responses. Objective: The purpose of this study is to determine the genotypic frequencies of CYP2D6 *1 (normal metabolizer), *4 (poor metabolizer) and *10 (intermediate metabolizer) variants among schizophrenic subjects and compared with control group from a sub-set of Karachi population. Method: Genomic deoxyribonucleic acid (DNA ) was extracted and amplified with CYP2D6*4 and *10 primers using polymerase chain reaction (PCR) and digested by Bacillus stereothermophilus (BstN1) and Hemophilus parahemolyticus (Hph1) restriction enzymes. The digested bands were identified as wild type or mutants and their genotypic frequencies were estimated statistically by Hardy-Weinberg equation (HWE) and analyzed further under non-parametric Chi-square test. Results: The results mentioned the frequencies of CYP2D6*1 wild allele (57%) which produces functional enzyme in normal subjects but CYP2D6*4 variant (9%) that produces non-functional enzyme and CYP2D6*10 allele (70%) produces altered enzyme with reduced activity that was most prevalent in schizophrenic patients. Conclusion : Genotyping of CYP2D6 alleles among schizophrenic patients indicated prevalence of *4 and *10 variants in Karachi population producing non-functional and reduced functional drugs metabolizing enzymes respectively that increases the incurability rate of schizophrenia. Therefore, CYP2D6 gene screening program should be conducted routinely in clinical practice to help clinicians to prescribing appropriate doses according to patient’s genotype and minimize the sufferings of schizophrenia. Discussion: In last, drug response is a complex phenomenon that is dependent on genetic and environmental factors. CYP2D6 polymorphism may un-cured the schizophrenia due to improper drug metabolism and protein-proteins interaction that may alter the antipsychotic drugs metabolism among patients with variable drug resposes. Gene testing system need to establish for analyzing maximum patient’s genotypes predicted with poor metabolizer, intermediate metabolizer and ultrarapid metabolizer for the adjustment of antipsychotic drugs.

scholarly journals Severe Adverse Drug Reactions to Quetiapine in Two Patients Carrying CYP2D6*4 Variants: A Case Report

2021 ◽  
Vol 22 (12) ◽  
pp. 6480
Author(s):  
Céline K. Stäuble ◽  
Markus L. Lampert ◽  
Thorsten Mikoteit ◽  
Martin Hatzinger ◽  
Kurt E. Hersberger ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Case Report ◽  
Adverse Drug Reactions ◽  
Active Metabolite ◽  
Hepatic Metabolism ◽  
Cytochrome P450 3A4 ◽  
Drug Reactions ◽  
Drug Induced ◽  
Potential Impact ◽  
Intermediate Metabolizer

We report two cases of patients who developed severe adverse drug reactions including persistent movement disorders, nausea, and vertigo during treatment with quetiapine at maximum daily doses ranging between 300 and 400 mg. The extensive hepatic metabolism of quetiapine is mainly attributed to cytochrome P450 3A4 (CYP3A4). However, there is recent evidence supporting the idea of CYP2D6 playing a role in the clearance of the quetiapine active metabolite norquetiapine. Interestingly, both patients we are reporting of are carriers of the CYP2D6*4 variant, predicting an intermediate metabolizer phenotype. Additionally, co-medication with a known CYP2D6 inhibitor and renal impairment might have further affected quetiapine pharmacokinetics. The herein reported cases could spark a discussion on the potential impact of a patient’s pharmacogenetic predisposition in the treatment with quetiapine. However, further studies are warranted to promote the adoption of pharmacogenetic testing for the prevention of drug-induced toxicities associated with quetiapine.

scholarly journals Endoscopic Fistulotomy – ‘The Suprapapillary Punch’: A Method of Access to the Bile Duct during ERCP

1994 ◽  
Vol 8 (1) ◽  
pp. 33-35
Author(s):  
Noel B Hershfield
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Endoscopic Retrograde Cholangiopancreatography ◽  
Biliary Tree ◽  
Usual Method ◽  
Endoscopic Retrograde ◽  
The Common ◽  
A Minor ◽  
Endoscopic Fistulotomy

Endoscopic retrograde cholangiopancreatography (ERCP) is established as the method of choice to investigate the biliary tree when obstruction is suspected. On rare occasions, the papilla cannot be entered because of anatomical or pathological abnormalities. This report describes endoscopic fistulotomy or the suprapapillary punch that has been carried out at the Foothills Hospital in Calgary, Alberta, on 30 of 623 patients referred for ERCP for conditions causing obstruction of the common bile duct or suspected obstruction of the common bile duct. The following communication also describes the method of suprapapillary punch or endoscopic fistulotomy. Results have been excellent with only one complication, a minor attack of pancreatitis after the procedure. In summary, the suprapapillary punch or fistulotomy is a safe and useful method for entering the common bile duct when access by the usual method is impossible.

scholarly journals Allele frequencies of single nucleotide polymorphisms of clinically important drug-metabolizing enzymes CYP2C9, CYP2C19, and CYP3A4 in a Thai population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rattanaporn Sukprasong ◽  
Sumonrat Chuwongwattana ◽  
Napatrupron Koomdee ◽  
Thawinee Jantararoungtong ◽  
Santirhat Prommas ◽  
...  
Keyword(s):  
Snp Genotyping ◽  
Allele Frequencies ◽  
Nucleotide Polymorphisms ◽  
Poor Metabolizer ◽  
Thai Population ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Genotyping Assay ◽  
Intermediate Metabolizer ◽  
Important Drug

AbstractPrior knowledge of allele frequencies of cytochrome P450 polymorphisms in a population is crucial for the revision and optimization of existing medication choices and doses. In the current study, the frequency of the CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2C19*6, CYP2C19*17, and CYP3A4 (rs4646437) alleles in a Thai population across different regions of Thailand was examined. Tests for polymorphisms of CYP2C9 and CYP3A4 were performed using TaqMan SNP genotyping assay and CYP2C19 was performed using two different methods; TaqMan SNP genotyping assay and Luminex x Tag V3. The blood samples were collected from 1205 unrelated healthy individuals across different regions within Thailand. Polymorphisms of CYP2C9 and CYP2C19 were transformed into phenotypes, which included normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM), and rapid metabolizers (RM). The CYP2C9 allele frequencies among the Thai population were 0.08% and 5.27% for the CYP2C9*2 and CYP2C9*3 alleles, respectively. The CYP2C19 allele frequencies among the Thai population were 25.60%, 2.50%, 0.10%, and 1.80% for the CYP2C19*2, CYP2C19*3, CYP2C19*6, and CYP2C19*17 alleles, respectively. The allele frequency of the CYP3A4 (rs4646437) variant allele was 28.50% in the Thai population. The frequency of the CYP2C9*3 allele was significantly lower among the Northern Thai population (P < 0.001). The frequency of the CYP2C19*17 allele was significantly higher in the Southern Thai population (P < 0.001). Our results may provide an understanding of the ethnic differences in drug responses and support for the utilization of pharmacogenomics testing in clinical practice.

scholarly journals Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

2016 ◽  
Vol 60 (4) ◽  
pp. 2492-2498 ◽  
Author(s):  
Marcelo Gomes Davanço ◽  
Michel Leandro Campos ◽  
Talita Atanazio Rosa ◽  
Elias Carvalho Padilha ◽  
Alejandro Henao Alzate ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Extended Release ◽  
Hydroxypropyl Methylcellulose ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Success ◽  
Preclinical Pharmacokinetics ◽  
Bioavailability Study

ABSTRACTBenznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.

Factors affecting the future of the Scottish hydrometric network

1987 ◽  
Vol 78 (4) ◽  
pp. 269-274 ◽  
Author(s):  
T. Poodle
Keyword(s):  
Data Acquisition ◽  
Computer Systems ◽  
Economic Recession ◽  
Data Standards ◽  
Factors Affecting ◽  
Economic Climate ◽  
A Minor ◽  
The Cost ◽  
Minor Extent

ABSTRACTThe Scottish Hydrometric Network consists of a number of river gauging stations which have been located at sites considered suitable to provide long term flow records. Economic recession has placed some stress on the gauging programme, and has given rise to extensive closures of gauging stations in England and, to a minor extent so far, in Scotland. The way in which the network became established provides a mixture of strengths and weaknesses which could have unpredictable consequences in an adverse economic climate. Changing technology provides some opportunity to reduce the cost of data acquisition and improve the deployment of manpower, while maintaining data standards. In these changing circumstances, particularly with extensive use of computer systems, it is important that standards are established for data returned to the Water Archive and that the network is not allowed to degenerate by default.

scholarly journals Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technology

2009 ◽  
Vol 59 (1) ◽  
pp. 15-30 ◽  
Author(s):  
Pramod Kumar ◽  
Sanjay Singh ◽  
Brahmeshwar Mishra
Keyword(s):  
Drug Release ◽  
Extended Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Tramadol Hydrochloride ◽  
Release Formulation ◽  
Extended Release Formulation

Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technologyExtended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media.In vivostudy was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax,tmax,AUC0-24,MRT) and relative bioavailability were calculated. Thein vitroandin vivoresults were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation.In vitro-in vivocorrelation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R= 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.

scholarly journals Effects of Diabetes Mellitus Induced by Alloxan on the Pharmacokinetics of Metformin in Rats: Restoration of Pharmacokinetic Parameters to the Control State by Insulin Treatment

2008 ◽  
Vol 11 (1) ◽  
pp. 88 ◽  
Author(s):  
Myung G. Lee ◽  
Young H Choi ◽  
Inchul Lee
Keyword(s):  
Diabetes Mellitus ◽  
Oral Administration ◽  
Protein Expression ◽  
Intravenous Administration ◽  
Insulin Treatment ◽  
Pharmacokinetic Parameters ◽  
Mrna Levels ◽  
Altered Pharmacokinetic ◽  
Intravenous And Oral Administration ◽  
Control State

To test the effect of insulin treatment on the pharmacokinetics of metformin in rats with diabetes mellitus induced by alloxan (DMIA rats). The following results were reported from other studies. Metformin was metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. In DMIA rats, the protein expression and mRNA levels of hepatic CYP2C11 and 3A1/2 decreased and increased, respectively. In rat model of diabetes mellitus induced by streptozotocin, the protein expression of hepatic CYP2D1 was not changed. The increase in hepatic CYP1A2, 2B1, and 2E1, and decrease in hepatic CYP2C11 in DMIA rats was returned to the controls by insulin treatment. METHODS. Metformin (100 mg/kg) was administered intravenously and orally to the control rats, DMIA rats, and DMIA rats with insulin treatment for 3 weeks (DMIA rats with insulin). RESULTS. After intravenous administration of metformin to the DMIA rats, the CLR and CLNR of the drug were significantly slower than the controls. After oral administration of metformin to the DMIA rats, the AUC of the drug was also significantly greater than the controls. After intravenous administration of metformin to the DMIA rats with insulin, the significantly slower CLNR of the drug in the DMIA rats was returned to the controls. The altered pharmacokinetic indices observed following intravenous and oral administration of metformin to DMIA rats returned to the control values in the DMIA rats with insulin. CONCLUSIONS. The significantly slower CLNR of metformin in the DMIA rats could be due to the decrease in hepatic CYP2C11 than the controls. The comparable CLNR of metformin between the DMIA rats with insulin and the control rats could be due to restoration of hepatic CYP enzyme changes in DMIA rats to the controls.

Cupressus arizonica (Arizona cypress).

2021 ◽  
Author(s):  
Sylvan Kaufman
Keyword(s):  
New World ◽  
Erosion Control ◽  
Economic Importance ◽  
Christmas Trees ◽  
Cupressus Arizonica ◽  
A Minor ◽  
Minor Extent

Abstract At present, in the New World, C. arizonica and its varieties are of low economic importance, but they are sometimes cut for fenceposts, fuelwood and lumber, and recently they have become popular as Christmas trees. By contrast, the Arizona cypress (C. arizonica var. arizonica) and the smooth cypress (C. arizonica var. glabra) are widespread in Europe and are used for landscaping, erosion control, windbreaks, and to a minor extent for lumber.

Sign in / Sign up

Export Citation Format

Share Document