scholarly journals Influence of concomitant medication on plasma concentration of amiodarone in patients with atrial fibrillation - A pilot study

2019 ◽  
Author(s):  
Maria Adriana Neag ◽  
Dana Maria Muntean ◽  
Alexandra Nacu ◽  
Adrian Catinean ◽  
Anca Farcas ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Plasma Concentration ◽  
Pilot Study ◽  
Prospective Observational Study ◽  
Beta Blockers ◽  
Plasma Concentrations ◽  
University Hospital ◽  
Significant Difference ◽  
Inflammatory Drugs ◽  
Concomitant Medications

Background. Although amiodarone is a drug with many side effects, it is one of the most commonly used drugs in the treatment and prophylaxis of supraventricular and ventricular arrhythmias. Aim. The purpose of this pilot study was to evaluate plasma concentrations of amiodarone in patients with atrial fibrillation (AF) and to identify possible drug-drug interactions between amiodarone and concomitant medications. Method. A prospective observational study was conducted in 27 consecutive patients treated with amiodarone from May to July 2017 in a Clinical University Hospital. The patients included met our inclusion criteria. HPLC-UV was the device used to determine the plasma concentration of amiodarone. Results. Only 51.8% of the patients had amiodarone plasma concentration within therapeutic interval (500-2500 ng/ml). The drugs associated to amiodarone in the therapeutic plan were diuretics, beta blockers, statins, antiplatelets, fluoroquinolones, non-steroidal anti-inflammatory drugs. We observed a statistically significant difference between the plasmatic concentrations of amiodarone in patients treated with furosemide vs. patients concomitantly treated with other drugs. Interactions between other mentioned drugs and amiodarone were not registered. We can report an underuse of amiodarone for more than 50% of the patients. Also, we found a significant interaction between furosemide and amiodarone, most likely through the interaction with MDR. Conclusion. Furosemide may influence the pharmacokinetics of P-gp-interfering drugs. However, the relevance of these findings needs to be confirmed and further research is needed to characterize the interaction between amiodarone and furosemide.

Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

2020 ◽  
Vol 21 (2) ◽  
pp. 126-131
Author(s):  
Bhuvanachandra Pasupuleti ◽  
Vamshikrishna Gone ◽  
Ravali Baddam ◽  
Raj Kumar Venisetty ◽  
Om Prakash Prasad
Keyword(s):  
Plasma Concentration ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Plasma Concentrations ◽  
Control Group ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Post Hoc ◽  
Hydrolysis Of ◽  
Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

scholarly journals Clopidogrel Pharmacokinetics in Malaysian Population Groups: The Impact of Inter-Ethnic Variability

2018 ◽  
Vol 11 (3) ◽  
pp. 74 ◽  
Author(s):  
Zaril Zakaria ◽  
Alan Fong ◽  
Raj Badhan
Keyword(s):  
Plasma Concentration ◽  
Plasma Concentrations ◽  
High Dose ◽  
Population Groups ◽  
Adjunct Treatment ◽  
Malaysian Population ◽  
Significant Difference ◽  
Target Plasma Concentration ◽  
Ethnic Variability ◽  
The Impact

Malaysia is a multi-ethnic society whereby the impact of pharmacogenetic differences between ethnic groups may contribute significantly to variability in clinical therapy. One of the leading causes of mortality in Malaysia is cardiovascular disease (CVD), which accounts for up to 26% of all hospital deaths annually. Clopidogrel is used as an adjunct treatment in the secondary prevention of cardiovascular events. CYP2C19 plays an integral part in the metabolism of clopidogrel to the active metabolite clopi-H4. However, CYP2C19 genetic polymorphism, prominent in Malaysians, could influence target clopi-H4 plasma concentrations for clinical efficacy. This study addresses how inter-ethnicity variability within the Malaysian population impacts the attainment of clopi-H4 target plasma concentration under different CYP2C19 polymorphisms through pharmacokinetic (PK) modelling. We illustrated a statistically significant difference (P < 0.001) in the clopi-H4 Cmax between the extensive metabolisers (EM) and poor metabolisers (PM) phenotypes with either Malay or Malaysian Chinese population groups. Furthermore, the number of PM individuals with peak clopi-H4 concentrations below the minimum therapeutic level was partially recovered using a high-dose strategy (600 mg loading dose followed by a 150 mg maintenance dose), which resulted in an approximate 50% increase in subjects attaining the minimum clopi-H4 plasma concentration for a therapeutic effect.

Vestibular rehabilitation using video gaming in adults with dizziness: a pilot study

2018 ◽  
Vol 132 (3) ◽  
pp. 202-206 ◽  
Author(s):  
J S Phillips ◽  
J Fitzgerald ◽  
D Phillis ◽  
A Underwood ◽  
I Nunney ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Trial ◽  
Pilot Study ◽  
Vestibular Rehabilitation ◽  
University Hospital ◽  
Control Group ◽  
Rehabilitation Protocol ◽  
Wii Fit ◽  
Significant Difference

AbstractObjective:To determine the effectiveness of vestibular rehabilitation using the Wii Fit balance platform, in adults with dizziness.Methods:A single-site prospective clinical trial was conducted in a university hospital in the UK. Forty patients with dizziness, who would normally be candidates for vestibular rehabilitation, were identified and considered as potential participants. Participants were randomised into either the treatment group (the Wii Fit group) or the control group (standard customised vestibular rehabilitation protocol). Participants were assessed over a 16-week period using several balance and quality of life questionnaires.Results:Both exercise regimes resulted in a reduction of dizziness and an improvement in quality of life scores over time, but no statistically significant difference between the two interventions was identified.Conclusion:This pilot study demonstrated that use of the Wii Fit balance platform resulted in a statistically significant improvement in balance function and quality of life. Furthermore, outcomes were comparable to a similar group of individuals following a standard customised vestibular rehabilitation protocol. The study provides useful information to inform the design and execution of a larger clinical trial.

scholarly journals Absorption of red clover isoflavones in human subjects: results from a pilot study

2010 ◽  
Vol 103 (11) ◽  
pp. 1569-1572 ◽  
Author(s):  
Ronald Maul ◽  
Sabine E. Kulling
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Pilot Study ◽  
Enzymatic Hydrolysis ◽  
Human Subjects ◽  
Plasma Concentrations ◽  
Red Clover ◽  
First Time ◽  
High Bioavailability ◽  
Present Pilot Study

In addition to soya-derived preparations, red clover-based dietary supplements have gained considerable interest as an alternative isoflavone (IF) source. While metabolism and bioavailability of the main IF from both sources have already been investigated, studies are still lacking on the biokinetic behaviour of IF, which are present in red clover in minor amounts. In the present pilot study, in which seven volunteers ingested a single dose of a commercial red clover dietary supplement, we focused on the absorption of three such IF, irilone (IRI), prunetin (PRUN) and pseudobaptigenin (PBAP). The compounds were measured as aglycones after enzymatic hydrolysis. A single intake of an amount of as low as 3·8 mg IRI (out of 38·8 mg IF in total) resulted in an IRI plasma concentration of 0·35 (sd 0·16) μm at 6.5 h post-ingestion. Compared to the plasma concentrations found for daidzein (0·39 μm) and genistein (0·06 μm), expected to be the main IF metabolites in plasma, the present findings indicate that IRI might possess a relatively high bioavailability. Furthermore, PRUN and PBAP were detected in human plasma for the first time.

scholarly journals Analgesic efficacy and associated plasma concentration of tramadol and O-desmethyltramadol following oral administration post ovariohysterectomy in dogs

2015 ◽  
Author(s):  
Elizabeth M Goudie-DeAngelis ◽  
Kerry J Woodhouse
Keyword(s):  
Plasma Concentration ◽  
Postoperative Pain ◽  
Pain Score ◽  
Short Form ◽  
Plasma Concentrations ◽  
Analgesic Efficacy ◽  
Pain Scale ◽  
Clinical Pain ◽  
Drug Plasma ◽  
Significant Difference

Tramadol is used in both human and veterinary medicine to treat postoperative pain. The purpose of this study was to evaluate tramadol as a sole postoperative analgesic and to compare drug plasma concentration to clinical pain score. A high or low dose of tramadol was randomly assigned and administered to 14 mixed breed female dogs after ovariohysterectomy. The Short-Form of the Glasgow Composite Measure Pain Scale was used for pain evaluation post-operatively. Plasma was collected for evaluation of tramadol and O-desmethyltramadol concentrations. The effect of weight and dose on pain scores as well as how pain score correlated with plasma concentration of tramadol and O-desmethyltramadol was evaluated. A significant difference in pain score was noted between doses when weight classes were pooled. The plasma concentrations did not correlate with pain score. Based on our results, the use of tramadol as a sole analgesic agent provides inadequate postoperative pain control.

Charge-Affected Transperitoneal Movement of Amino Acids in Capd

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 88-90 ◽  
Author(s):  
Toshiyuki Nakao ◽  
Makoto Ogura ◽  
Hajime Takahashi ◽  
Tomonari Okada
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Dwell Time ◽  
Plasma Concentrations ◽  
University Hospital ◽  
Blood Samples ◽  
Significant Difference ◽  
Molecular Charge ◽  
Solute Movement ◽  
Positively Charged

Our objective was to investigate the influence of molecular charge on transperitoneal solute movement in continuous ambulatory peritoneal dialysis (CAPD). Tests of peritoneal equilibration were performed. Two liters of 2.27% or 2.5% glucose CAPD dialysate were infused and the dialysate samples were taken after 2 hr and 4 hr, and blood samples were obtained after 4-hr dwell time. Dialysate-to-plasma concentrations ratios (DIP) were calculated for creatinine (Cr) and three amino acids with almost the same molecular weight but quite different charges: glutamic acids (Glu: negatively charged), glutamine (Gin: near neutrally charged), and lysine (Lys: positively charged). The setting was a university hospital. There were 23 stable CAPD patients with a mean age of 56.5±9.5 years and a mean CAPD duration of 15.2±19.4 months. DIP ratio of Glu was much lower than those of Gin, Lys and Cr at both 2 hr and 4 hr (p < 0.01), and DIP of Lys was significantly lower than that of Gin (p < 0.01). There was no significant difference of DIP between Gin and Cr. The order of transperitoneal mobility among the three amino acids was Gin > Lys > Glu. Transperitoneal movement of solutes in CAPD is influenced by molecular charge, the movement of negatively charged solutes is most remarkably retarded in cases of amino acids.

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.

scholarly journals Influence of ABCB1 Gene Polymorphism on Rivaroxaban Blood Concentration and Hemorrhagic Events in Patients With Atrial Fibrillation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Wang ◽  
Min Chen ◽  
Hui Chen ◽  
Fang Wang
Keyword(s):  
Atrial Fibrillation ◽  
Blood Concentration ◽  
Plasma Concentrations ◽  
Multiple Comparisons ◽  
Bleeding Events ◽  
Abcb1 Gene ◽  
Management Protocol ◽  
Significant Difference ◽  
Hemorrhagic Events ◽  
Trough Concentrations

Background and Objectives: Genetic data on the pharmacokinetics of rivaroxaban and identification of factors that affect its biotransformation, distribution, and excretion will allow for generation of algorithms for personalized use of this drug in patients with atrial fibrillation (AF). Here we tested the effects of ABCB1 (ATP-binding cassette subfamily B member 1) polymorphisms on the valley rivaroxaban blood concentration and on the frequency of hemorrhagic events in patients with AF and propose a personal anticoagulation therapy management protocol.Patients and Methods: This is a retrospective study. We enrolled Mongolian descent patients who met the criteria from May 2018 to August 2019 in Beijing and Fujian. Clinical data on gender, height, weight, liver and kidney functions, drug trough concentration, and drug dosage were collected; we recorded the bleeding events until 6 months after initiating the medication. ABCB1 single nucleotide polymorphisms including rs1128503, rs1045642, and rs4148738 were identified. After reaching the steady state of plasma concentration, the peripheral blood was collected to detect the trough rivaroxaban plasma concentrations before the next medication.Results: We included 155 patients in this study including 81 men and 74 women, with an average age of 71.98 ± 10.72 years. The distribution of ABCB1 genotypes conformed to the Hardy–Weinberg equilibrium. Multiple comparisons between wild (TT) and mutant (CT and CC) genotypes at the rs1045642 locus showed no significant differences of rivaroxaban trough concentrations (TT vs. CT, p = 0.586; TT vs. CC, p = 0.802; and CT vs. CC, p = 0.702). Multiple comparison between wild (TT) and mutant (CC) genotypes at the rs1128503 locus revealed a significant difference of rivaroxaban trough concentrations (TT vs. CC, p = 0.0421). But wild (TT) vs mutant (CT) genotypes and mutant CT vs mutant CC genotypes at the rs1128503 locus showed no significant differences of rivaroxaban trough concentrations (TT vs. CT, p = 0.0651; TT vs. CT, p = 0.6127). Multiple comparisons between wild (GG) and mutant (AG and AA) genotypes at the rs4148738 locus showed no significant differences of rivaroxaban trough concentrations (GG vs. AG, p = 0.341; GG vs. AA, p = 0.612; AG vs. AA, p = 0.649). There was no significant correlation between ABCB1 gene variation loci rs1045642, rs1128503, rs4148738 and bleeding events.Conclusion: rs1128503 locus variations are correlated with the serum concentration of rivaroxaban in patients of Mongolian descent. But no significant correlation between rs1128503 locus variations and bleeding events were obtained.

scholarly journals The accuracy of undergraduate paramedic students in measuring blood pressure: A pilot study

2014 ◽  
Vol 11 (2) ◽  
Author(s):  
Malcolm Boyle ◽  
Brett Williams ◽  
Simon Sawyer
Keyword(s):  
Blood Pressure ◽  
Pilot Study ◽  
Measurement Accuracy ◽  
Prospective Observational Study ◽  
Random Number ◽  
Study Data ◽  
Convenience Sample ◽  
Significant Difference ◽  
Random Number Table ◽  
Clinical Measures

IntroductionMeasurement of a blood pressure (BP) in the prehospital setting is one of many basic skills required of a paramedic.  Assessment of BP is also one of several clinical measures that determines the patient’s treatment and possibly the receiving hospital. The objective of this study was to determine the accuracy of undergraduate paramedic students in taking a BP in a non-clinical setting.MethodsThis was a prospective observational study using the Laerdal VitalSim mannequin with the BP volume and strength set at mid range values to test the accuracy of BP measurement.  There were 62 third year Monash University paramedic students available for the study.  We used three different BP ranges, a low, normal and high BP.  Each student was randomly assigned the first and second BP by using a random number table.  Each student was permitted one practice BP prior to the study data collection commencing.  Ethics approval was granted.ResultsA convenience sample of 26 (42%) third year undergraduate paramedic students participated.  69% were female, with 46% being between 21 and 25 years of age.  Two students, nurses, had previous BP measurement experience.  There were six, four and four students who accurately measured the high, normal and low BP respectively.  There was a statistical significant difference between the actual and student measured BP for the high systolic BP (p=0.004), normal systolic BP (p=0.023), and low systolic (p=0.019) and diastolic (p=0.004) BP.ConclusionThis pilot study has highlighted that third year Monash University paramedic student’s lack BP measurement accuracy in a non-clinical setting.  This pilot study has highlighted the need for a review of how the teaching of BP measurement is undertaken within the curriculum.

scholarly journals Laboratory Assessment of the Anticoagulant Activity of Apixaban in Patients With Nonvalvular Atrial Fibrillation

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 194S-201S ◽  
Author(s):  
Elias Kyriakou ◽  
Konstantinos Katogiannis ◽  
Ignatios Ikonomidis ◽  
George Giallouros ◽  
Georgios K. Nikolopoulos ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Thrombin Generation ◽  
Anticoagulant Activity ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Plasma Concentrations ◽  
Nonvalvular Atrial Fibrillation ◽  
Laboratory Assessment ◽  
Thrombin Generation Assay ◽  
Significant Difference

Our aim is to determine the most appropriate laboratory tests, besides anti-factor Xa (anti-FXa) chromogenic assays, to estimate the degree of anticoagulation with apixaban and compare it with that of rivaroxaban in real-world patients. Twenty patients with nonvalvular atrial fibrillation treated with apixaban 5 mg twice daily and 20 patients on rivaroxaban 20 mg once daily were studied. Conventional coagulation tests, thrombin generation assay (TGA), and thromboelastometry (nonactivated TEM [NATEM] assay) were performed in the 40 patients and 20 controls. The anti-FXa chromogenic assays were used to measure apixaban and rivaroxaban plasma levels. The NATEM measurements showed no significant difference between the 2 groups of patients. Concerning TGA, endogenous thrombin potential (ETP) was significantly decreased in patients on rivaroxaban as compared to those treated with apixaban ( P < .003). A statistically significant, strong inverse correlation between apixaban plasma concentrations and ETP ( P < .001) was observed. Apixaban significantly reduces ETP compared to controls, but to a lesser extent than rivaroxaban. Thrombin generation assay might provide additional information on apixaban exposure, which is required in order to individualize treatment especially for patients with a high bleeding risk. Our findings have to be further investigated in studies with larger sample sizes, in the entire range of apixaban exposure, with other direct oral anticoagulants, and in relation to clinical outcomes.

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