- Clinical Pharmacology Driven Translational Research to Optimize Bedside Therapeutics of Sotalol Therapy. [Journal Article]
- CTClin Transl Sci 2019 Jul 22
- Oral Sotalol used in adults for sinus rhythm-control is initiated at 80 mg BID and titrated to a maximum safe dose. FDA recommends QTc monitoring for at least 3 days, until steady-state exposure of t…
Oral Sotalol used in adults for sinus rhythm-control is initiated at 80 mg BID and titrated to a maximum safe dose. FDA recommends QTc monitoring for at least 3 days, until steady-state exposure of the drug is reached, before patient discharge, which can significantly impact the total cost of treatment. To design an accelerated intravenous sotalol loading and maintenance therapy that will reduce the hospital length of stay and to also evaluate the pharmacoeconomic impact in a hospital setting. Pharmacokinetic (PK) simulations of plasma sotalol concentrations versus times profiles were performed to determine the optimal intravenous/oral transition regimen. A cost minimization analysis from the health sector perspective was conducted to assess the cost savings for these proposed accelerated regimens. For a chosen target dose of 120 mg BID, two infusions, 40 mg over 1 hour and 20 mg over 0.5 hour, each followed up by an evaluation of QTc, can be administered followed immediately by the target oral maintenance dose of 120 mg at the end of the second infusion. Consequently, steady-state exposure and therefore steady-state QTc are obtained on the first day of therapy, facilitating an earlier hospital discharge. Two and one-day mean total cost of -$3,123 [95% confidence interval (CI), -$3,640, -$2,607] -$4,820 [95% CI, -$5,352, -$4,288] were observed for this strategy. We are proposing an intravenous to oral transition strategy for sotalol that has the potential to significantly reduce cost and increase patient convenience. This article is protected by copyright. All rights reserved.
- Screen printed carbon electrode sensor with thiol graphene quantum dots and gold nanoparticles for voltammetric determination of solatol. [Journal Article]
- HHeliyon 2019; 5(6):e01984
- This work, a highly selective and sensitive sensor is described for voltammetric determination of the sotalol (SOT). The dual actions of sotalol lead to reductions in the automaticity of myocardial c…
This work, a highly selective and sensitive sensor is described for voltammetric determination of the sotalol (SOT). The dual actions of sotalol lead to reductions in the automaticity of myocardial cells and in conduction through the atrioventricular node. Drug analysis has an extensive impact on public health. The molecularly imprinted sensor was constructed by modifying a screen printed carbon electrode (SPCE) with thiol graphene quantum dots (GQD-SH) and gold nanoparticles (AuNPs). Under optimal conditions the nanotools has a dynamic range that covers the 0.1-250 μM SOT concentration range, and the detection limit is 0.035 μM. This is lower than any of the previously reported methods. The MIP-sensor also exhibited excellent selectivity, good stability and adequate reproducibility for the detection of the SOT over its structural analogs. The prepared sensor was successfully applied to the measurement of SOT in various real samples including tablet and human blood serum.
- Single and mixture toxicity of four pharmaceuticals of environmental concern to aquatic organisms, including a behavioral assessment. [Journal Article]
- CChemosphere 2019 Jun 26; 235:373-382
- Pharmaceuticals are frequently detected in aquatic environments as mixtures and can cause toxic effects to non-target organisms. We aimed to evaluate the single and mixture effects of the pharmaceuti…
Pharmaceuticals are frequently detected in aquatic environments as mixtures and can cause toxic effects to non-target organisms. We aimed to evaluate the single and mixture effects of the pharmaceuticals metformin, bisoprolol, ranitidine and sotalol using Daphnia similis and Danio rerio. In addition, we aimed to test the predictive accuracy of the mathematical models concentration addition and independent action and to evaluate the nature of the possible toxicological interactions among these pharmaceuticals using the combination index-isobologram model. The acute toxicity of these four pharmaceuticals individually and of their binary mixtures were evaluated using the D. similis tests. Developmental and behavioral effects induced by the pharmaceuticals in quaternary mixtures were evaluated using D. rerio embryos. We observed that most of the binary mixture effects were in the zone between the effects predicted by the concentration addition and the independent action model. The combination index-isobologram model showed to be adequate to describe the nature of possible interactions occurring between the combined pharmaceuticals. Developmental and behavioral acute adverse effects seem not to be induced by the joint action of the quaternary mixture of the evaluated pharmaceuticals on D. rerio embryos, at the concentrations at which they are usually found in surface fresh waters. However, from the results obtained with D. similis, we can conclude that assessing the ecological risk based on the effects of individual pharmaceuticals can underestimate the risk level posed by these environmental contaminants.
- Telemetered common marmosets is useful for the assessment of electrocardiogram parameters changes induced by multiple cardiac ion channel inhibitors. [Journal Article]
- JTJ Toxicol Sci 2019; 44(7):441-457
- The objective of this study is to assess the response of telemetered common marmosets to multiple cardiac ion channel inhibitors and to clarify the usefulness of this animal model in evaluating the e…
The objective of this study is to assess the response of telemetered common marmosets to multiple cardiac ion channel inhibitors and to clarify the usefulness of this animal model in evaluating the effects of drug candidates on electrocardiogram (ECG). Six multiple cardiac ion channel inhibitors (sotalol, astemizole, flecainide, quinidine, verapamil and terfenadine) were orally administered to telemetered common marmosets and changes in QTc, PR interval and QRS duration were evaluated. Drugs plasma levels were determined to compare the sensitivity in common marmosets to that in humans. QTc prolongation was observed in the marmosets dosed with sotalol, astemizole, flecainide, quinidine, verapamil and terfenadine. PR prolongation was noted after flecainide and verapamil administration, and QRS widening occurred following treatment with flecainide and quinidine. Drugs plasma levels associated with ECG changes in marmosets were similar to those in humans, except for verapamil-induced QTc prolongation. Verapamil-induced change is suggested due to body temperature decrease. These results indicate that telemetered common marmoset is a useful animal for evaluation of the ECG effects of multiple cardiac ion channel inhibitors and the influence of body temperature change should be considered in the assessment.
- Association Between Serum Potassium Levels and Short-Term Mortality in Patients With Atrial Fibrillation or Flutter Co-treated With Diuretics and Rate- or Rhythm-Controlling Drugs. [Journal Article]
- EHEur Heart J Cardiovasc Pharmacother 2019 Jul 02
- CONCLUSIONS: In addition to hypo- and hyperkalemia, low and high normal range potassium levels were associated with increased 90-day mortality risk in AF patients co-treated with diuretics and rate- or rhythm-controlling drugs. These associations were independent of rate- or rhythm-controlling drugs.
- Influence of water depth and season on the photodegradation of micropollutants in a free-water surface constructed wetland receiving treated wastewater. [Journal Article]
- CChemosphere 2019 Jun 24; 235:260-270
- Micropollutants such as pharmaceutical products and pesticides are still present in treated wastewater. Several of these compounds are photoactive, either by direct or indirect photodegradation. An i…
Micropollutants such as pharmaceutical products and pesticides are still present in treated wastewater. Several of these compounds are photoactive, either by direct or indirect photodegradation. An innovative on-site experimental protocol was designed to investigate the contribution of photodegradation processes to eliminate micropolluants in constructed wetland (CW). The solar photodegradation of 23 organic micropollutants was studied using in situ photoreactors at different depths. A CW-photodegradation model was designed and calibrated to further scrutinize the contribution of direct and indirect photodegradation processes in the elimination of micropollutants. The results show that photodegradation is most effective in the first 10 cm of the water column. A classification of micropollutants in 3 groups was developed to characterize their photodegradation. A significant increase of the half-life by direct photodegradation was observed in winter compared to summer due to a lower light intensity in winter. On the opposite, for direct + indirect photodegradation, no significant difference was observed between seasons. The decrease in light intensity in winter was compensated by higher nitrates concentration which promoted the formation of hydroxyl radicals and increased indirect photodegradation. The CW-photodegradation model successfully simulated the measured concentrations for direct and indirect photodegradation for 23 micropolluants. Nonetheless, it overestimated the indirect photodegradation with hydroxyl radicals when using default parameter values derived for surface waters. Hence, the consumption of hydroxyl radicals was increased by a factor of 20 for treated water. This model highlighted the predominance of direct photodegradation in the elimination of all micropollutants, except sotalol for the winter campaign.
- Metal organic framework HKUST-1 modified with carboxymethyl-β-cyclodextrin for use in improved open tubular capillary electrochromatographic enantioseparation of five basic drugs. [Journal Article]
- MAMikrochim Acta 2019 Jun 21; 186(7):462
- This work shows that the metal organic framework (MOF) HKUST-1 of type Cu3(BTC)2 (also referred to as MOF-199; a face-centered-cubic MOF containing nanochannels) is a most viable coating for use in e…
This work shows that the metal organic framework (MOF) HKUST-1 of type Cu3(BTC)2 (also referred to as MOF-199; a face-centered-cubic MOF containing nanochannels) is a most viable coating for use in enantioseparation in capillary electrochromatography (CEC). A HKUST-1 modified capillary was prepared and characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectra, elemental analysis and thermogravimetric analysis. CEC-based enantioseparation of the basic drugs propranolol (PRO), esmolol (ESM), metoprolol (MET), amlodipine (AML) and sotalol (SOT) was performed by using carboxymethyl-β-cyclodextrin as the chiral selector. Compared with a fused-silica capillary, the resolutions are improved (ESM: 1.79; MET: 1.80; PRO: 4.35; SOT: 1.91; AML: 2.65). The concentration of chiral selector, buffer pH value, applied voltage and buffer concentration were optimized, and the reproducibilities of the migration times and Rs values were evaluated. Graphical abstract Schematic presentation of the preparation of a HKUST-1@capillary for enantioseparation of racemic drugs. Cu(NO3)2 and 1,3,5-benzenetricarboxylic acid (BTC) were utilized to prepare the HKUST-1@capillary. Then the capillary was applied to construct capillary electrochromatography system with carboxymethyl-β-cyclodextrin (CM-β-CD) for separation of basic racemic drugs.
- Maternal monitoring and safety considerations during antiarrhythmic treatment for fetal supraventricular tachycardia. [Review]
- OMObstet Med 2019; 12(2):66-75
- Fetal tachycardia is a rare complication during pregnancy. After exclusion of maternal and fetal conditions that can result in a secondary fetal tachycardia, supraventricular tachycardia is the most …
Fetal tachycardia is a rare complication during pregnancy. After exclusion of maternal and fetal conditions that can result in a secondary fetal tachycardia, supraventricular tachycardia is the most common cause of a primary sustained fetal tachyarrhythmia. In cases of sustained fetal supraventricular tachycardia, maternal administration of digoxin, flecainide, sotalol, and more rarely amiodarone, is considered. As these medications have the potential to cause significant adverse effects, we sought to examine maternal safety during transplacental treatment of fetal supraventricular tachycardia. In this narrative review we summarize the literature addressing pharmacologic properties, monitoring, and adverse reactions associated with medications most commonly prescribed for transplacental therapy of fetal supraventricular tachycardia. We also describe maternal monitoring practices and adverse events currently reported in the literature. In light of our findings, we provide clinicians with a suggested maternal monitoring protocol aimed at optimizing safety.
- Linking microbial diversity and population dynamics to the removal efficiency of pharmaceutically active compounds (PhACs) in an anaerobic/anoxic/aerobic (A2O) system. [Journal Article]
- CChemosphere 2019; 233:828-842
- The removal efficiencies (REs) of nineteen pharmaceutically active compounds (PhACs) (six antibiotics-clarithromycin, ofloxacin, sulfadiazine, sulfamethazine, sulfamethoxazole and trimethoprim -, fou…
The removal efficiencies (REs) of nineteen pharmaceutically active compounds (PhACs) (six antibiotics-clarithromycin, ofloxacin, sulfadiazine, sulfamethazine, sulfamethoxazole and trimethoprim -, four β-blockers -atenolol, metoprolol, propranolol and sotalol-, two antihypertensives/diuretics -furosemide and hydrochlorothiazide-, three lipid regulators -bezafibrate, fenofibrate and gemfibrozil-, and four psychiatric medications -carbamazepine, diazepam, lorazepam and paroxetine) were ascertained in a pilot-scale anaerobic/anoxic/aerobic (A2O) system treating urban wastewater, long term operated during two experimental phases using different sets of environmental conditions and operating parameters. Illumina MiSeq sequencing was used to investigate the structure, diversity and population dynamics of bacteria, archaea and fungi communities in the activated sludge. The results showed that mixed liquor suspended solids (MLSS) and food-to-microorganisms ratio (F/M) were operational parameters significantly influencing the REs of five of the analyzed PhACs in the A2O system. Biota-environment (BIO-ENV) analysis revealed strong correlations between population shifts of the activated sludge community and the REs of PhACs of the different pharmaceutical families. Increased REs of clarithromycin, furosemide, bezafibrate and gemfibrozil were concomitant to higher relative abundances of bacterial phylotypes classified within the Rhodobacteraceae and Sphingomonadaceae (Alphaproteobacteria), while those of Betaproteobacteria, Chloroflexi and Methanomethylovorans (Euryarchaea) correlated positively with the REs of up to seven PhACs belonging to different therapeutic groups.
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- Successful radiofrequency catheter ablation of a premature ventricular contraction triggering ventricular fibrillation in a patient with short QT syndrome. [Case Reports]
- HCHeartRhythm Case Rep 2019; 5(5):262-265