scholarly journals Pharmacokinetic Disposition of Amiodarone When Given with an Intralipid Rescue Strategy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 539
Author(s):  
Sean N. Avedissian ◽  
Michelle Pham ◽  
Medha D. Joshi ◽  
Marc H. Scheetz ◽  
Ashkan Salamatipour ◽  
...  
Keyword(s):  
High Performance ◽  
Therapeutic Index ◽  
Hplc Method ◽  
Control Group ◽  
Swine Model ◽  
Narrow Therapeutic Index ◽  
Time Curve ◽  
Target Organs ◽  
Acute Overdose ◽  
Intravenous Amiodarone

While the antiarrhythmic drug amiodarone is commonly used in clinical practice, it has a narrow therapeutic index that can lead to acute overdose. One proposed method to deal with this toxicity is lipid emulsion therapy, which may potentially quench the free amiodarone in blood and prevent its further distribution to target organs and tissues. In this study, we utilize an established swine model to examine the effects of Intralipid™ (IL) administration for acute amiodarone toxicity. A total of 14 pigs received an overdose of intravenous amiodarone. After twenty minutes, half of the pigs (n = 7) received IL while the control group (n = 7) received normal saline. Serum concentrations of amiodarone were then analyzed using a validated high-performance liquid chromatography (HPLC) method. Noncompartmental pharmacokinetic analyses were performed on the observed concentrations. There were no statistical differences in the area under the concentration time curve (6 h) or clearance, but there was a difference in the half-life between the two groups (3.12 vs. 0.85 h, p = 0.01). The administration of IL did not statistically change the overall exposure of amiodarone in the blood in the first 6 h; however, trends toward prolonged blood retention in the IL group were seen.

THE COMBINATION OF CLASSICAL TESTS AND METHODS OF CHROMATOGRAPHY FOR LABORATORY DIAGNOSTICS OF CUSHING’S SYNDROME OF DIFFERENT GENESIS

2020 ◽  
Vol 65 (7) ◽  
pp. 418-423
Author(s):  
Z. R. Shafigullina ◽  
L. I. Velikanova ◽  
N. V. Vorokhobina ◽  
E. V. Malevanaya ◽  
E. G. Strelnikova ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Sensitivity And Specificity ◽  
Cushing’S Syndrome ◽  
High Performance ◽  
Cushing's Syndrome ◽  
Hplc Method ◽  
Gas Chromatography Mass Spectrometry ◽  
Control Group ◽  
Laboratory Diagnostics ◽  
Free Cortisol

Immunochemical methods of analysis are traditionally used for diagnosis of various forms of Cushing’s syndrome (CS). In the presence of boundary values of hormonal parameters, doubtful situations, a combination of changes both in pituitary and in adrenal glands, it is useful to determine additional differential diagnostic criteria for the diagnosis of various forms of CS. Urinary steroid profiles (USP) were analyzed by gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) for 38 females with adrenal Cushing’s syndrome (CSA), 42 females with pituitary CS (CSP) and 25 healthy females (control group). An increase of free cortisol/free cortisone ratio in the urine (UFF/UFE) for CSP patients in comparison of CSA was obtained by HPLC method. Decreased urinary excretion of UFF and UFE by more than 60% after the 8 mg dexamethasone suppression test had 100% sensitivity and specificity of more than 90% for the diagnosis of CSP. GC-MS method in patients with CSA and CSG revealed the peculiarities of androgens, progestins and glucocorticoids metabolism which leaded to obtain specific USP for CS of different genesis. Increased urinary excretions of dehydroepiandrosterone and its metabolites, metabolites of androstenedione, the ratio of sum of cortisol and cortisone tetrahydrometabolites to tetrahydro-11-deoxycortisol (more then 36) in CSP patients compared with CSA are additional signs for differential diagnosis of these diseases. The combination of classical tests and USP obtained by HPLC and GC-MS methods increased the sensitivity and specificity of differential diagnosis of CSA and CSP.

scholarly journals Linezolid Inhibited Synthesis of ATP in Mitochondria: Based on GC-MS Metabolomics and HPLC Method

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Xuemei Ye ◽  
Aifang Huang ◽  
Xianqin Wang ◽  
Congcong Wen ◽  
Lufeng Hu ◽  
...  
Keyword(s):  
Serum Concentration ◽  
High Performance ◽  
Multidrug Resistant ◽  
Hplc Method ◽  
Control Group ◽  
Sprague Dawley ◽  
High Group ◽  
Atp Concentration ◽  
Sprague Dawley Rats ◽  
Serious Infections

Linezolid has been widely used in serious infections for its effective inhibiting effect against multidrug-resistant gram-positive pathogens. However, linezolid caused severe adverse reactions, such as thrombocytopenia, anaemia, optic neuropathy, and near-fatal serotonin syndrome. In order to investigate the toxicity of linezolid, twenty-four Sprague-Dawley rats were randomly divided into: control group (n=7), low-group (n=8), and high-group (n=9). The rats of low-group and high-group were given by gavage with linezolid 60 and 120 mg/kg/day for 7 days, respectively. The serum concentration of linezolid was determined by high performance liquid chromatography (HPLC); blood metabolic change was analyzed by gas chromatography-mass spectrometer (GC-MS). Adenosine triphosphate (ATP) concentration in HepG2-C3A after being cultured with linezolid was determined by HPLC. The results showed that there were six metabolites and nine metabolites had statistical differences in low-group and high-group (P<0.05). The trimethyl phosphate was the most significant indicator in those changed metabolites. Except for d-glucose which was slightly increased in low-group, octadecanoic acid, cholest-5-ene, hexadecanoic acid, α-linolenic acid, eicosapentaenoic acid, 9,12-Octadecadienoic acid, and docosahexaenoic acid were all decreased in low-group and high-group. ATP concentration was decreased in HepG2-C3A after cultured with linezolid. In conclusion, the toxicity of linezolid is related to its serum concentration. Linezolid may inhibit the synthesis of ATP and fatty acid.

scholarly journals Comparative Performances of Flubendazole and Albendazole in Cystic Echinococcosis:Ex VivoActivity, Plasma/Cyst Disposition, and Efficacy in Infected Mice

2011 ◽  
Vol 55 (12) ◽  
pp. 5861-5867 ◽  
Author(s):  
Laura Ceballos ◽  
Celina Elissondo ◽  
Sergio Sánchez Bruni ◽  
Guillermo Denegri ◽  
Carlos Lanusse ◽  
...  
Keyword(s):  
Cystic Echinococcosis ◽  
High Performance ◽  
Ex Vivo ◽  
Control Group ◽  
Efficacy Study ◽  
Active Molecule ◽  
Time Curve ◽  
Content Type ◽  
Drug Of Choice ◽  
Scanning Electron

ABSTRACTThe need to identify improved therapy against cystic echinococcosis (CE) has motivated pharmacology-based research. The comparative pharmacological performances of the benzimidazole compounds flubendazole (FLBZ) and albendazole (ABZ) were addressed here. The goals of the work were as follows: (i) to evaluate theex vivoactivities of FLBZ, ABZ, and their respective metabolites againstEchinococcus granulosusprotoscoleces, (ii) to compare the plasma and cyst disposition kinetics for the two drugs in infected mice, and (iii) to compare the clinical efficacies of FLBZ and ABZ against CE in mice. For theex vivostudy,E. granulosusprotoscoleces were incubated with FLBZ, reduced FLBZ (R-FLBZ), ABZ, and ABZ-sulfoxide (ABZSO) (10 nmol/ml). Protoscolex viability was monitored by the methylene blue exclusion test and scanning electron microscopy (SEM). For the pharmacokinetic study, BALB/c mice with CE were allocated to two different groups and orally treated with either FLBZ or ABZ (5 mg/kg of body weight), both formulated as a cyclodextrin-based solution. Blood and cyst samples were taken up to 12 h posttreatment and analyzed by high-performance liquid chromatography (HPLC). For the efficacy study, CE-infected BALB/c mice were divided into three groups: the unmedicated control group and the FLBZ- and ABZ-treated groups. Oral treatments were performed twice a day during 25 days. After treatment, all animals were killed and the weight of the cysts was recorded. Loss of protoscolex viability was observed after drug incubation. FLBZ was detected in plasma (area under the concentration-versus-time curve [AUC] = 1.8 μg·h/ml) and cysts (AUC = 0.3 μg·h/g) collected from treated infected animals. Conversely, ABZSO was the only active molecule measured in plasma (AUC = 4.4 μg·h/ml) and cysts (AUC = 1.5 μg·h/g) after ABZ treatment. FLBZ induced a 90% reduction in cyst weight in comparison to those collected from untreated control mice (P< 0.05). However, no differences in cyst weight were observed between the ABZ-treated (8.2 g) and unmedicated control (10.5 g) groups. Due to these results, we consider flubendazole to have great potential to become a drug of choice in the treatment of cystic echinococcosis.

Stability of Warfarin in Spiked-Saliva Using the Fluorometric HPLC Method

2021 ◽  
Vol 1162 ◽  
pp. 180-190
Author(s):  
Vitarani Dwi Ananda Ningrum ◽  
Levia Chitra Dewi ◽  
Ari Wibowo
Keyword(s):  
Biological Fluid ◽  
Therapeutic Index ◽  
Storage Condition ◽  
Hplc Method ◽  
Therapeutic Drug ◽  
Excitation Wavelength ◽  
Narrow Therapeutic Index ◽  
Standard Curve ◽  
Thaw Cycle ◽  
Freeze Thaw Cycle

Warfarin is an anticoagulant with a narrow therapeutic index ranging from 1-10 µg/mL as well as the ability to distribute into saliva. Therefore, saliva can be selected as an alternative biological fluid in warfarin bioanalysis of therapeutic drug monitoring (TDM) since it is easier and more acceptable, particularly among pediatric and geriatric patients. Stability is an important part of the bioanalysis of warfarin in TDM services. This study aims to conduct a stability of warfarin in spiked-saliva using Fluorometric HPLC at an excitation wavelength of 310 nm and 390 nm emission. Analytes were separated using phosphate buffer:methanol as the mobile phase with a flow rate of 1.0 mL/min and an injection volume of 20µL as well as 150mmx4.5mm C18 as the stationary phase. The standard curve of warfarin with a concentration range of 0-20 ng/mL resulted in a correlation coefficient of 0.999. This study showed that the warfarin stock solution was stable at both 25°C and 4°C for 24 hours and 21 days, respectively. Meanwhile, warfarin in the saliva matrix also remained stable at 25°C for 24 hours and in a storage condition of -20°C for 21 days. In this research, the sample of saliva from patients administered with warfarin that has been treated with a maximum freeze-thaw cycle of 3-fold or 24 hours after preparation could consistently provide accurate data to be used as an approach to making a decision on dosage adjustment and diagnosis of warfarin toxicity in the clinical setting.

Comparison of Assay Procedures Used to Measure Total and Unbound Concentrations of Quinidine

DICP ◽  
1989 ◽  
Vol 23 (12) ◽  
pp. 999-1004 ◽  
Author(s):  
Ronald A. Wooding-Scott ◽  
Inger M. Darling ◽  
Richard L. Slaughter
Keyword(s):  
High Performance ◽  
Equilibrium Dialysis ◽  
Free Fraction ◽  
Therapeutic Index ◽  
Hplc Method ◽  
Total Serum ◽  
Acceptable Error ◽  
Wide Variability ◽  
Serum Quinidine ◽  
Pharmacokinetic Behavior

Individualized quinidine dosing through the assessment of serum concentrations is warranted because of the wide variability observed in its pharmacokinetic behavior and its reported narrow therapeutic index. The free fraction of quinidine also varies widely. Thus the development of procedures that could be widely used to determine quinidine free concentrations would be highly desirable. It was the purpose of this study to evaluate several procedures available to determine total serum quinidine concentrations (rate nephelometry [ICS], homogenous enzyme immunoassay [EMIT], and high-performance liquid chromatography [HPLC]). Furthermore, in samples from 46 patients, equilibrium dialysis and ultrafiltration procedures were compared for their ability to estimate quinidine free fraction. Finally, unbound concentrations of quinidine were compared using a modified EMIT procedure and a standard HPLC method to quantitate quinidine in ultrafiltrates from patient samples. For the measurement of total quinidine concentrations, reasonable agreement was seen when EMIT and ICS systems were compared with HPLC (ICS = 1.03 · HPLC +0.96, r=0.93;EMIT= 1.08 · HPLC + 0.38, r=0.93) The mean errors, however, for these procedures were high (ICS +70 percent, range +7 to +233 percent; EMIT + 35 percent, range 0 to 110 percent). Quinidine free fractions (QFF) determined by equilibrium dialysis (E) and ultrafiltration (U) showed good agreement (QFF(U) = 1.11 · QFF(E) + 0.0; r = 0.96). Unbound quinidine concentration determined by EMIT analysis of ultrafiltrate substantially overestimated the values obtained by HPLC analysis (mean error by EMIT 104 ± 59 percent). It is concluded that HPLC is the method of choice for determining both total and unbound serum quinidine concentrations. The EMIT procedure on average produces acceptable error for the measurement of total quinidine concentrations; however, errors greater than 100 percent do occur. Thus, caution should be used when interpreting the results of the EMIT procedure. For determining unbound concentrations the EMIT produces unacceptable error and the HPLC method should be used to obtain reliable estimates of free quinidine concentrations.

scholarly journals Impact of insulin adsorption in various container during hyperkalemia treatment

2021 ◽  
Author(s):  
Thomas Robert ◽  
Patrice Vanelle ◽  
Philippe Brunet ◽  
Nathalie Martin ◽  
Stéphane Burtey ◽  
...  
Keyword(s):  
High Performance ◽  
Therapeutic Index ◽  
Insulin Delivery ◽  
Insulin Concentration ◽  
Narrow Therapeutic Index ◽  
Intravenous Insulin ◽  
Time Average ◽  
Clinically Significant ◽  
Glucose Therapy ◽  
Treatment Procedures

Abstract Background The insulin-glucose therapy in hyperkalemia treatment had a narrow therapeutic index for a safe and efficient use. We assess the variability of the effective delivered insulin under conditions used in the setting of hyperkalemia treatment. Methods A range of simulated insulin infusions was studied using different containers (bag or syringes) according of the different hyperkalemia treatment procedures of our institution. Insulin concentration was assayed using a chromatographic method on an automatic high-performance liquid chromatography. We calculated the effective delivered insulin and compared the time-average of percentage delivered insulin (TAdi) between all the procedures. Results The TAdi is significantly decreased to 63.3% of the expected insulin delivery in the polyurethane (PE) bag compared to allover container. The procedure duration and the insulin concentration influenced the variability of the insulin delivery in the PE and glass (G) bag. The polyvinyl chloride (PVC) bag have the highest TAdi at 93.8% without significant variation during the time. TAdi reach around 90% of the expected insulin with all the syringe procedure without variation according the solute used to dilute insulin. Conclusions Clinically significant variations in intravenous insulin delivery occur in the setting of hyperkalemia treatment according to the container. The use of propylene syringe limits the insulin delivery variation. In the future, clinical studies on hyperkalemia treatment by insulin-glucose therapy should detailed the procedure precisely.

scholarly journals Evaluation of the Effects of Astragalus membranaceus on the Pharmacokinetics of Pemetrexed Disodium and Gemcitabine in Rats by a Simple High-Performance Liquid Chromatography/UV Method

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Zixuan Chu ◽  
Zhiyuan Wang ◽  
Teng Liu ◽  
Shan Xiong ◽  
Bin Liu
Keyword(s):  
High Performance ◽  
Therapeutic Strategy ◽  
Rat Plasma ◽  
Hplc Method ◽  
Astragalus Membranaceus ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Pemetrexed Disodium ◽  
Gradient Mode

Combination therapy is opted as a potential therapeutic strategy for cancer treatment. Astragalus membranaceus combined with pemetrexed disodium or gemcitabine could reinforce the overall effects and alleviate the adverse effects. To investigate the effects of Astragalus membranaceus on the pharmacokinetics of pemetrexed disodium and gemcitabine, a HPLC method for simultaneous determination of pemetrexed disodium and gemcitabine in rat plasma was developed and validated. Chromatographic separation was achieved on a C18 column using a gradient mode containing water (containing 20 mM NaH2PO4 and 0.1% FA) and methanol at a flow rate of 0.8 mL/min. The specificity, linearity, recovery, stability, precision, and accuracy of the HPLC method were all validated. The rats were pretreated with Astragalus extract at the dosage of 3 g/kg for 20 consecutive days until we commence studying the pharmacokinetics of pemetrexed disodium or gemcitabine. There were no significant differences in pharmacokinetic parameters of pemetrexed disodium between the Astragalus extract treatment group and the control group. However, AUC, MRT, and Cl of gemcitabine were changed dramatically after treating with Astragalus extract (p<0.05). The AUC(0−t), AUC(0−∞), and MRT of gemcitabine decreased from 15747.12 ± 497.11 to 12312.41 ± 594.21 mg/L·min, 15976.18 ± 511.33 to 12489.59 ± 682.01 mg/L·min, and 97.83 ± 5.82 to 84.37 ± 2.79 min, respectively. The Cl of gemcitabine increased from 0.019 ± 0.0067 to 0.024 ± 0.0013 L/min/kg. The results showed that the pretreatment of Astragalus extract could exert an influence on the pharmacokinetic characteristics of gemcitabine in rats.

scholarly journals Therapeutic Drug Monitoring of Linezolid: a Retrospective Monocentric Analysis

2010 ◽  
Vol 54 (11) ◽  
pp. 4605-4610 ◽  
Author(s):  
Federico Pea ◽  
Mario Furlanut ◽  
Piergiorgio Cojutti ◽  
Francesco Cristini ◽  
Eleonora Zamparini ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
High Performance ◽  
Drug Exposure ◽  
Plasma Concentrations ◽  
Hplc Method ◽  
Therapeutic Drug ◽  
Time Curve ◽  
Standard Dosage ◽  
Wide Variability

ABSTRACT The objective of the present retrospective observational study carried out in patients receiving a standard dosage of linezolid and undergoing routine therapeutic drug monitoring (TDM) was to assess the interindividual variability in plasma exposure, to identify the prevalence of attainment of optimal pharmacodynamics, and to define if an intensive program of TDM may be warranted in some categories of patients. Linezolid plasma concentrations (trough [C min] and peak [C max] levels) were analyzed by means of a high-performance liquid chromatography (HPLC) method, and daily drug exposure was estimated (daily area under the plasma concentration-time curve [AUC24]). The final database included 280 C min and 223 C max measurements performed in 92 patients who were treated with the fixed 600-mg dose every 12 h (q12h) intravenously (n = 58) or orally (n = 34). A wide variability was observed (median values [interquartile range]: 3.80 mg/liter [1.75 to 7.53 mg/liter] for C min, 14.70 mg/liter [10.57 to 19.64] for C max, and 196.08 mg·h/liter [144.02 to 312.10 mg·h/liter] for estimated AUC24). Linezolid C min was linearly correlated with estimated AUC24 (r 2 = 0.85). Optimal pharmacodynamic target attainment (defined as C min of ≥2 mg/liter and/or AUC24/MIC90 ratio of >80) was obtained in about 60 to 70% of cases, but potential overexposure (defined as C min of ≥10 mg/liter and/or AUC24 of ≥400 mg·h/liter) was documented in about 12% of cases. A significantly higher proportion of cases with potential overexposure received cotreatment with omeprazole, amiodarone, or amlodipine. Our study suggests that the application of TDM might be especially worthwhile in about 30% of cases with the intent of avoiding either the risk of dose-dependent toxicity or that of treatment failure.

scholarly journals Therapeutic Drug Monitoring of Cytotoxic Drugs

2020 ◽  
Vol 10 (02) ◽  
pp. 284-291
Author(s):  
Qutaiba Ahmad Al Khames Aga ◽  
Yazan A. Bataineh ◽  
Hala Mousa Sbaih
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Malignant Tumors ◽  
Therapeutic Index ◽  
Review Article ◽  
Cytotoxic Drugs ◽  
Therapeutic Drug ◽  
Narrow Therapeutic Index ◽  
Time Curve ◽  
The Common

The majority of anticancer drugs are recognized with a narrow therapeutic index, the area under the plasma levels vs. time curve (AUC) is the common pharmacokinetic (PK) parameter, which utilizes specifically for cytotoxic drugs. Therapeutic drug monitoring (TDM) approach in these drugs has never been completely applied due to different reasons, for example, the use of combination chemotherapies for different malignant tumors, and the behavior of intracellular compounds; it is possible to eliminate these limitations by using specific concentrations of cytotoxic drugs and measure AUC after certain conditions. In this review article, we discussed the common TDM parameters, methods of analysis, and some of drug interactions for a group of cytotoxic drugs.

Evaluation of Gloriosa superba for Yield Attributing Characters and Quantification of Colchicine Originated from Different Agro Climatic Zones of Tamil Nadu and Andhra Pradesh

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Arun Kumar P. ◽  
Elangaimannan R.
Keyword(s):  
Seed Yield ◽  
Tamil Nadu ◽  
High Performance ◽  
Andhra Pradesh ◽  
Crop Improvement ◽  
Mean Value ◽  
Hplc Method ◽  
Gloriosa Superba ◽  
Climatic Zones ◽  
Colchicine Alkaloid

The study was conducted to evolve Gloriosa superba for yield characters and alkalodi content for selecting elite genotypes for comercial exploitatio n. The genotypes were sowm in Variyankaval village, Udayarpalayam taluk of Ariyalur district, Tamil Nadu. The highest mean value for fresh and dry seed yield was observed in Chittor local. The genotype Mulanur local has recorded the highest mean value for number of pods per plant and number of seeds per pod and Arupukotai local excelled the general mean for the traits seeds per pod, fresh and dry seed yield and also for tuber characters. An investigation was carried out to quantify the colchicine (alkaloid) present in tubers by High Performance Liquid Chromatography (HPLC) method. The genotypes collected from Arupukotai recorded the highest colchicine content (0.760 mg/g) followed by Chittoor (0.578 mg/g) and Mulanur (0.496 mg/g) and there by these three genotypes were utilized for further crop improvement.

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