Pharmacokinetic Analysis of Theophylline to Assess Noncompliance in Therapy

2002 ◽  
Vol 36 (5) ◽  
pp. 835-838
Author(s):  
Hiroki Konishi ◽  
Takayuki Nakatsuka ◽  
Michiaki Yoshida ◽  
Shinji Tamaki ◽  
Tokuzo Minouchi ◽  
...  
Keyword(s):  
Antihypertensive Drugs ◽  
Absorption Capacity ◽  
Pharmacokinetic Analysis ◽  
Liquid Form ◽  
Tablet Form ◽  
Oral Theophylline ◽  
Novel Approach ◽  
Patient Noncompliance ◽  
Theophylline Absorption ◽  
Apparent Bioavailability

OBJECTIVE: To report a case showing patient noncompliance, supported by outcomes of pharmacokinetic analysis of theophylline as a surrogate drug. CASE SUMMARY: A 45-year-old woman with severe hypertension was treated with a variety of oral antihypertensive drugs, but there was no improvement in her elevated blood pressure. Since we suspected that her intestinal drug absorption capacity was impaired, a theophylline absorption test was performed. When oral theophylline was given to the patient in tablet form, the apparent bioavailability was only 20%, which agreed with our hypothesis. However, the bioavailability of theophylline given in liquid form was almost 100%, and theophylline in tablet form was confirmed to be fully bioavailable when the test was performed under supervision by medical staff. DISCUSSION: The almost complete bioavailability of oral theophylline indicated that there was no impairment in intestinal absorption capacity. The low bioavailability of theophylline observed after tablet administration in the first trial was apparently a result of noncompliance, because the staff did not supervise administration to ensure that tablets were swallowed. Thus, the low response to antihypertensive therapy was attributed to patient noncompliance in taking the drugs, despite her insistence to the contrary. CONCLUSIONS: The use of theophylline was a novel approach to evaluating the absorbability of orally administered drugs in a patient suspected of poor compliance with therapy. A great difference in theophylline bioavailability between the supervised and unsupervised trials was strongly indicative of patient noncompliance. The possibility of impaired absorption was virtually ruled out.

scholarly journals Oral liquid levothyroxine treatment at breakfast: a mistake?

2014 ◽  
Vol 170 (1) ◽  
pp. 95-99 ◽  
Author(s):  
Carlo Cappelli ◽  
Ilenia Pirola ◽  
Elena Gandossi ◽  
Annamaria Formenti ◽  
Maurizio Castellano
Keyword(s):  
Thyroid Hormone ◽  
Liquid Form ◽  
Coffee Intake ◽  
Tablet Form ◽  
Significant Difference ◽  
Oral Liquid ◽  
Euthyroid Patient ◽  
Tablet Formulations ◽  
Levothyroxine Treatment

ObjectiveTaking levothyroxine (l-T4) with coffee or with water followed by coffee intake within a few minutes results in poor TSH response in many patients. T4is available in tablet form worldwide, but novel formulations in soft gel capsule or liquid form are now available.DesignWe fortuitously identified a euthyroid patient who wrongly consumed liquidl-T4with coffee at breakfast; after changing the time of consumption to 30 min before breakfast, no change in TSH, free T4(fT4), and free tri-iodothyronine (fT3) concentrations was observed. Once the first patient was identified, additional stable euthyroid patients who consumed liquidl-T4with coffee were identified.MethodsPatients were recruited by searching our ‘thyroid patients’ database. All the patients on liquidl-T4treatment were contacted by phone to ask them whether they tookl-T4at breakfast. We identified 54 patients who were submitted to TSH, fT4, and fT3evaluation, with the indication that the same dosage ofl-T4be consumed 30 min before breakfast. We determined their TSH, fT4, and fT3concentrations after 3 and 6 months again.ResultsNo significant difference in thyroid hormone concentrations was observed in patients when they consumedl-T4at breakfast or when they consumed it 30 min before breakfast for 3 and 6 months (TSH: 2.5±1.1 vs 2.5±1.1 and 2.4±1.1 mIU/l respectively, fT4: 12.4±2.4 vs 12.5±2.4 and 12.3±2.1 pg/ml respectively, and fT3: 3.4±0.6 vs 3.4±0.6 and 3.3±0.5 pg/ml respectively).ConclusionOral liquidl-T4formulations could diminish the problem ofl-T4malabsorption caused by coffee when using traditional tablet formulations.

scholarly journals Joint Population Pharmacokinetic Analysis of Zidovudine, Lamivudine, and Their Active Intracellular Metabolites in HIV Patients

2011 ◽  
Vol 55 (7) ◽  
pp. 3423-3431 ◽  
Author(s):  
C. Bazzoli ◽  
H. Bénech ◽  
E. Rey ◽  
S. Retout ◽  
D. Salmon ◽  
...  
Keyword(s):  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Intracellular Metabolites ◽  
Drug Concentrations ◽  
The Mean ◽  
Intracellular Concentrations ◽  
Apparent Bioavailability

ABSTRACTThe population pharmacokinetic parameters of zidovudine (AZT), lamivudine (3TC), and their active intracellular metabolites in 75 naïve HIV-infected patients receiving an oral combination of AZT and 3TC twice daily as part of their multitherapy treatment in the COPHAR2-ANRS 111 trial are described. Four blood samples per patient were taken after 2 weeks of treatment to measure drug concentrations at steady state. Plasma AZT and 3TC concentrations were measured in 73 patients, and among those, 62 patients had measurable intracellular AZT-TP and 3TC-TP concentrations. For each drug, a joint population pharmacokinetic model was developed and we investigated the influence of different covariates. We then studied correlations between the mean plasma and intracellular concentrations of each drug. A one-compartment model with first-order absorption and elimination best described the plasma AZT concentration, with an additional compartment for intracellular AZT-TP. A similar model but with zero-order absorption was found to adequately described concentrations of 3TC and its metabolite 3TC-TP. The half-lives of AZT and 3TC were 0.81 h (94.8%) and 2.97 h (39.2%), respectively, whereas the intracellular half-lives of AZT-TP and 3TC-TP were 10.73 h (69%) and 21.16 h (44%), respectively. We found particularly a gender effect on the apparent bioavailability of AZT, as well as on the mean plasma and intracellular concentrations of AZT, which were significantly higher in females than in males. Relationships between mean plasma drug and intracellular metabolite concentrations were also highlighted both for AZT and for 3TC. Simulation with the model of plasma and intracellular concentrations for once- versus twice-daily regimens suggested that a daily dosing regimen with double doses could be appropriate.

A Novel Approach of Chitosan Additive to Remove Formaldehyde from Building Materials

2011 ◽  
Vol 335-336 ◽  
pp. 1174-1180
Author(s):  
Huang Chin Wang ◽  
Sy Yuan Kang ◽  
Chao Heng Tseng ◽  
Wen Cheng Shau ◽  
Zhi Yang Chen
Keyword(s):  
Removal Efficiency ◽  
Indoor Air ◽  
Building Materials ◽  
Urea Formaldehyde ◽  
Absorption Capacity ◽  
Structural Element ◽  
Carcinogenic Substance ◽  
Novel Approach ◽  
Before And After ◽  
Industrial Standards

Formaldehyde (HCHO) which emitted from building materials, such as plywood and adhesive, is a carcinogenic substance in indoor air. Chitosan is produced from the structural element in the exoskeleton of crustaceans (such as crabs and shrimp), and has the ability to absorb HCHO. In this study, the HCHO removal efficiency by chitosan additives was evaluated for two building materials - adhesive and plywood. The experiments were performed in a small chamber based on the method of Japanese Industrial Standards (JIS) A1901 to evaluate the HCHO emission from adhesive and plywood before and after the application of chitosan additives. Both the HCHO concentration in the chamber and the HCHO emission factor of two adhesives, urea-formaldehyde (UF) resin and Poly Vinyl Acetate (PVAC) resin, were reduced from 0.02~0.21 ppm and 0.12~1.05 mg/m2h to 0~0.14 ppm and 0.12~0.63 mg/m2h after using chitosan additives. The best HCHO removal efficiency was adding 9% chitosan additives in the adhesives. The amount of absorbed HCHO is proportional to the amount of chitosan additives, and approximate 0.02 mg of HCHO can be absorbed by per mg of chitosan additive (i.e. absorption capacity 0.02 g HCHO/g Chitosan).

The Texas Cryogenic Oxy-Fuel Cycle (TCO): A Novel Approach to Power Generation With CO2 Options

2012 ◽  
Author(s):  
Jason Gatewood ◽  
Jeff Moore ◽  
Marybeth Nored ◽  
Klaus Brun ◽  
Vishwas Iyengar
Keyword(s):  
Co2 Emissions ◽  
Oil Recovery ◽  
High Pressures ◽  
Fuel Cycle ◽  
Thermodynamic Cycle ◽  
Liquid Form ◽  
Power Requirement ◽  
Long Term Storage ◽  
Novel Approach ◽  
The Individual

A novel oxy-fuel based power cycle is presented that combines conventional oxy-fuel cycle technology with novel mixed gaseous compression and liquid pumping of CO2 to produce both useable power and provide transportable CO2 for transportation via pipeline for use in sequestration or enhanced oil recovery (EOR). CO2 emissions reduction is a central focus of climate change initiatives. Therefore, it is desired to have a power plant process cycle that reduces CO2 emissions associated with producing power. Once captured CO2 must be transferred to a sequestration site for long term storage or utilized in EOR operations. Recent research has demonstrated that CO2 is most efficiently transported as a liquid at high pressures via pipelines. A Cryogenic Oxy-Fuel cycle will be presented that captures all CO2 produced during combustion and inherently converts that CO2 to a sequestration-ready state that can be immediately placed into transportation pipelines and stored at the desired sequestration site. The proposed cycle deviates from conventional cycles in that during part of the process the CO2 is in cooled liquid form which allows; 1) Decreased power demand to increase the CO2 pressure because pumping has lower power requirement than compression, 2) The take-off of the CO2 is optimized for pipeline transport and no further compression or expansion is required, and 3) A high overall thermodynamic cycle efficiency can be reached with relatively low firing temperatures in the oxy-burner (around 1000°F). This significantly simplifies the combustor and expander designs required for the process. Additional benefits of the cycle include predicted efficiencies near state of the art IGCC’s, applicability to multiple fuel sources, and cost reduction associated with reduced component sizes utilized in the cycle. This presentation will focus on the overall operational and technological requirements of the novel cycle, a breakdown of the individual components utilized, and simulations demonstrating predicted performance. Technological challenges of implementing a working version of the cycle will be discussed and suggested development required for overcoming the challenges will be presented. This paper will include recent research and development of an oxy-fuel combustor utilized in the cycle as well as implementation of compression and pumping apparatus of recent development.

scholarly journals APPLICATION OF WATER BEADS AS A NOVEL AND SIMPLE SORBENT FOR SMARTPHONE-BASED COLORIMETRIC DETERMINATION OF IRON IN WATER

Química Nova ◽  
2021 ◽  
Author(s):  
Cristina Adamo ◽  
Ayandra Jungera ◽  
Dosil Jesus
Keyword(s):  
Colorimetric Detection ◽  
High Water ◽  
Absorption Capacity ◽  
Colorimetric Determination ◽  
Iron Ions ◽  
Novel Approach ◽  
Phenanthroline Complex ◽  
Lake Waters ◽  
Orange Color

This work proposes a novel approach for colorimetric assays using ubiquitous and inexpensive water beads (WBs) made of a superabsorbent polymer (sodium polyacrylate). The high-water absorption capacity by the WBs was exploited for the preconcentration of iron ions from samples of tap, well, and lake waters. Moreover, the WBs also worked as a substrate for colorimetric detection of iron by the classical reaction of formation of Fe(II)-phenanthroline complex. Digital images acquired with a smartphone were used to obtain the color intensity of the WBs containing the orange color complex. The WBs were able to uptake and preconcentrate iron ions, allowing colorimetric detection with good linearity (R2 = 0.9978) and limits of detection (LOD) and quantification (LOQ) of 0.02 and 0.07 mg L-1, respectively. The proposed method provided recoveries ranging from 93 to 111% for a sample of well water spiked with 0.15 mg L-1 of iron.

scholarly journals Compatibility-tuned distribution of nanoparticles in co-continuous rubber structures toward microwave absorption enhancement

RSC Advances ◽  
2017 ◽  
Vol 7 (2) ◽  
pp. 1093-1100 ◽  
Author(s):  
Lefan Li ◽  
Pengfei Zhao ◽  
Yongyue Luo ◽  
Heping Yu ◽  
Jinlong Tao ◽  
...  
Keyword(s):  
Carbon Black ◽  
Natural Rubber ◽  
Microwave Absorption ◽  
Absorption Capacity ◽  
Epoxidized Natural Rubber ◽  
Absorption Enhancement ◽  
Rubber Composites ◽  
Rubber Blends ◽  
Novel Approach ◽  
Natural Rubber Composites

Carbon black incorporated natural rubber/epoxidized natural rubber composites with enhanced microwave absorption capacity have been designed by a novel approach of compatibility-tuned nanoparticles distribution in co-continuous rubber blends.

scholarly journals MUCOADHESIVE BUCCAL FILMS: A NOVEL APPROACH FOR THE DELIVERY OF ANTI-HYPERTENSIVE DRUGS

2021 ◽  
pp. 12-21
Author(s):  
ADESH YELAVE ◽  
GEETA BHAGWAT
Keyword(s):  
Drug Delivery ◽  
Antihypertensive Drugs ◽  
Hot Extrusion ◽  
Systemic Circulation ◽  
Oral Dosage ◽  
Novel Approach ◽  
Systemic Bioavailability ◽  
Buccal Drug Delivery ◽  
And Performance ◽  
Buccal Films

The buccal drug delivery system is a prominent route of administration for drug delivery through the buccal mucosa. It is rich in blood supply with more surface area for rapid absorption as well as provides direct entry of drugs from the site of application into the systemic circulation through the jugular vein. Buccal drug delivery systems consist of various approaches such as lozenges, wafers, gels, microparticles, patches or films from which mucoadhesive buccal film is an attractive dosage form in terms of flexibility and high systemic bioavailability. Since most of the antihypertensive drugs show first-pass metabolism which leads to less oral bioavailability generally up to 20–50%. Thus, incorporation of antihypertensive drugs in mucoadhesive buccal films using mucoadhesive polymers can provide higher systemic bioavailability. The films can be formulated using various techniques such as solvent casting method and hot extrusion melt method. These films can be evaluated based on various characteristics to determine their efficacy and performance such as tensile strength, mucoadhesion residence time, and kinetic release data analysis. They have various advantages over conventional solid oral dosage forms, hence are preferable for the preparation of antihypertensive drug-loaded buccal films. Mucoadhesive buccal films of antihypertensive drugs can also provide controlled drug delivery with enhanced bioavailability.

Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity

2019 ◽  
Vol 476 (24) ◽  
pp. 3705-3719 ◽  
Author(s):  
Avani Vyas ◽  
Umamaheswar Duvvuri ◽  
Kirill Kiselyov
Keyword(s):  
Oxidative Stress ◽  
Head And Neck ◽  
Transcriptional Activation ◽  
Platinum Resistance ◽  
Mrna Levels ◽  
Strong Positive Correlation ◽  
Platinum Compounds ◽  
Copper Chelation ◽  
Novel Approach ◽  
Cancer Models

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.

Collecting Words: A Clinical Example of a Morphology-Focused Orthographic Intervention

2020 ◽  
Vol 51 (3) ◽  
pp. 544-560 ◽  
Author(s):  
Kimberly A. Murphy ◽  
Emily A. Diehm
Keyword(s):  
Written Language ◽  
Morphological Knowledge ◽  
English Orthography ◽  
Word Level ◽  
Novel Approach ◽  
Language Pathology ◽  
The One ◽  
Critical Intervention ◽  
Reading And Spelling ◽  
Reading And Spelling Difficulties

Purpose Morphological interventions promote gains in morphological knowledge and in other oral and written language skills (e.g., phonological awareness, vocabulary, reading, and spelling), yet we have a limited understanding of critical intervention features. In this clinical focus article, we describe a relatively novel approach to teaching morphology that considers its role as the key organizing principle of English orthography. We also present a clinical example of such an intervention delivered during a summer camp at a university speech and hearing clinic. Method Graduate speech-language pathology students provided a 6-week morphology-focused orthographic intervention to children in first through fourth grade ( n = 10) who demonstrated word-level reading and spelling difficulties. The intervention focused children's attention on morphological families, teaching how morphology is interrelated with phonology and etymology in English orthography. Results Comparing pre- and posttest scores, children demonstrated improvement in reading and/or spelling abilities, with the largest gains observed in spelling affixes within polymorphemic words. Children and their caregivers reacted positively to the intervention. Therefore, data from the camp offer preliminary support for teaching morphology within the context of written words, and the intervention appears to be a feasible approach for simultaneously increasing morphological knowledge, reading, and spelling. Conclusion Children with word-level reading and spelling difficulties may benefit from a morphology-focused orthographic intervention, such as the one described here. Research on the approach is warranted, and clinicians are encouraged to explore its possible effectiveness in their practice. Supplemental Material https://doi.org/10.23641/asha.12290687

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