scholarly journals Bioequivalence metrics for absorption rates: linearity, specificity, sensitivity

2019 ◽  
Vol 89 (1) ◽  
pp. 17-21
Author(s):  
István Vincze ◽  
László Endrényi ◽  
László Tóthfalusi
Keyword(s):  
Multiple Dose ◽  
Kinetic Feature ◽  
Point Estimates ◽  
Sensitivity Curves ◽  
Dose Concentration ◽  
Rate Of Absorption ◽  
Generic Products ◽  
Sensitivity Specificity ◽  
Concentration Curves ◽  
Extent Of Absorption

Aims:In order to ensure the therapeutic equivalence of generic products, it would be important to contrast measures additional to Cmax in order to assess differences in absorption rates.  Our aim was to compare partial AUC (PAUC), Swing, and PTF to Cmax in terms of sensitivity, specificity and linearity under identical kinetic conditions. Methods:Single-dose and multiple-dose concentration curves were generated assuming one-compartment models. Kinetic sensitivity curves were obtained by gradually changing the absorption rate constant and keeping all other parameters fixed. Results:A metric should reflect specifically the investigated kinetic feature (e.g., the rate of absorption), be linearly related to it, and should exhibit high kinetic sensitivity.  Cmax is related nonlinearly to the rate of absorption, is nonspecific to it (reflects also the extent of absorption as well as the rates of disposition processes), lacks kinetic sensitivity even following a single administration.  Compared to Cmax, PAUC was always more sensitive under every investigated condition.  Swing and PTF showed high kinetic sensitivity but, in contrast to PAUC, they could be evaluated only in multiple-dose studies.  Conclusion:Under identical conditions, different metrics provide widely differing point estimates.  Differences in kinetic sensitivity among bioequivalence metrics should be accounted for when results of different metrics are compared.

Stimulation of abomasal flow in sheep with buffer infusions per abomasum and effects of same on certain aspects of intestinal function

1988 ◽  
Vol 39 (6) ◽  
pp. 1121 ◽  
Author(s):  
DE Margan
Keyword(s):  
Small Intestine ◽  
Volatile Fatty Acids ◽  
Sodium Citrate ◽  
Mineral Salts ◽  
Proximal Half ◽  
Abomasal Infusion ◽  
Gastric Juice Secretion ◽  
Rate Of Absorption ◽  
Flow Changes ◽  
Extent Of Absorption

Infusion into the abomasum of sheep of a mixture of volatile fatty acids partially neutralized with sodium hydroxide (VFA salts) markedly increased the rates of flow of liquor and chloride from the abomasum to the small intestine; buffered mineral salts comprising sodium bicarbonate, sodium citrate and either disodium or dipotassium orthophosphate consistently produced a similar but smaller response. Thcre was little or no effect of the infusions on rumen or omasal outflow. By contrast, infusion of VFA in acid form had no effect on abomasal liquor and chloride flow and the infusion of sodium chloride did not effect liquor flow. The pH of abomasal digesta either decreased slightly or was unchanged when VFA salts wcre infused, but increased with infusion of mineral buffer salts. It is concluded that gastric secretion is markedly affected by the buffering capacity of the digesta entering the abomasum. The VFA entering the abomasum in digesta were estimated to be responsible for the secretion of as much as 60% of the chloride secreted into the organ. High rates of abomasal secretion, induced by intra-abomasal infusion of VFA salts, increased both (i) the amount of digesta in the abomasum and small intestine, (ii) the extent of absorption of calcium and magnesium distal to the omasum, and (iii) absorption from the small intestine of water, chloride and VFA, while decreasing (i) the pH of digesta in some sections of the small intestine and (ii) marker residence time in the proximal half of the small intestine. The rates of flow of both liquor and chloride from the abomasum, together with pH of abomasal digesta, progressively increased with age in animals aged 6, 10 and 30 months; they were still larger in other animals aged 54 months. By contrast, no consistent trends with age were observed with VFA and chloride concentrations in rumen liquor or the flow of metabolites from the rumen. The flow changes are suggested to be the result of changes in gastric juice secretion with age, stimulated at least in part by a corresponding decrease in the rate of absorption of buffering substances in the omasum and/or abomasum.

Investigation on the need of multiple dose bioequivalence studies for prolonged-release generic products

2012 ◽  
Vol 423 (2) ◽  
pp. 321-325 ◽  
Author(s):  
Alfredo García-Arieta ◽  
Susana Morales-Alcelay ◽  
Marta Herranz ◽  
José María de la Torre-Alvarado ◽  
Antonio Blázquez-Pérez ◽  
...  
Keyword(s):  
Multiple Dose ◽  
Prolonged Release ◽  
Generic Products

scholarly journals Development and Greenness Assessment of HPLC Method for Studying the Pharmacokinetics of Co-Administered Metformin and Papaya Extract

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 375
Author(s):  
Mohamed A. Abdelgawad ◽  
Mohammed Elmowafy ◽  
Arafa Musa ◽  
Mohammad M. Al-Sanea ◽  
AbdElAziz A. Nayl ◽  
...  
Keyword(s):  
Blood Glucose Control ◽  
Internal Standard ◽  
Essential Elements ◽  
Hplc Method ◽  
Pharmacokinetic Analysis ◽  
Diabetic Patients ◽  
Maximum Plasma ◽  
Rp Hplc ◽  
Rate Of Absorption ◽  
Extent Of Absorption

Foods with medical value have been proven to be beneficial, and they are extensively employed since they integrate two essential elements: food and medication. Accordingly, diabetic patients can benefit from papaya because the fruit is low in sugar and high in antioxidants. An RP-HPLC method was designed for studying the pharmacokinetics of metformin (MET) when concurrently administered with papaya extract. A mobile phase of 0.5 mM of KH2PO4 solution and methanol (65:35, v/v), pH = 5 ± 0.2 using aqueous phosphoric acid and NaOH, and guaifenesin (GUF) were used as an internal standard. To perform non-compartmental pharmacokinetic analysis, the Pharmacokinetic program (PK Solver) was used. The method’s greenness was analyzed using two tools: the Analytical GREEnness calculator and the RGB additive color model. Taking papaya with MET improved the rate of absorption substantially (time for reaching maximum concentration (Tmax) significantly decreased by 75% while maximum plasma concentration (Cmax) increased by 7.33%). The extent of absorption reduced by 22.90%. Furthermore, the amount of medication distributed increased (30.83 L for MET concurrently used with papaya extract versus 24.25 L for MET used alone) and the clearance rate rose by roughly 13.50%. The results of the greenness assessment indicated that the method is environmentally friendly. Taking papaya with MET changed the pharmacokinetics of the drug dramatically. Hence, this combination will be particularly effective in maintaining quick blood glucose control.

scholarly journals Development and Validation of the Elecsys Anti-SARS-CoV-2 Immunoassay as a Highly Specific Tool for Determining Past Exposure to SARS-CoV-2

2020 ◽  
Vol 58 (10) ◽  
Author(s):  
Peter Muench ◽  
Simon Jochum ◽  
Verena Wenderoth ◽  
Beatus Ofenloch-Haehnle ◽  
Michael Hombach ◽  
...  
Keyword(s):  
Blood Donors ◽  
Diagnostic Testing ◽  
High Sensitivity ◽  
Cross Reactivity ◽  
Point Estimates ◽  
Wide Range ◽  
Vesicular Stomatitis ◽  
Sensitivity Specificity ◽  
Development And Validation ◽  
Roche Diagnostics

ABSTRACT The Elecsys Anti-SARS-CoV-2 immunoassay (Roche Diagnostics) was developed to provide accurate, reliable detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated sensitivity, specificity, cross-reactivity, and agreement with a vesicular stomatitis virus-based pseudoneutralization assay for the Elecsys Anti-SARS-CoV-2 immunoassay. Sensitivity and agreement between Elecsys Anti-SARS-CoV-2 immunoassay and pseudoneutralization assay measurements were evaluated using samples from patients with PCR-confirmed SARS-CoV-2 infection, a majority of whom were hospitalized. Specificity was evaluated using samples from routine diagnostic testing/blood donors collected before December 2019 and thus deemed negative for SARS-CoV-2-specific antibodies. Cross-reactivity was evaluated using samples containing a wide range of potentially cross-reacting analytes, purchased from commercial vendors. For sensitivity and specificity, point estimates and 95% confidence intervals (CIs) were calculated. Agreement between the Elecsys Anti-SARS-CoV-2 immunoassay and the pseudoneutralization assay was calculated. The sensitivity of the Elecsys Anti-SARS-CoV-2 immunoassay in patients with prior PCR-confirmed SARS-CoV-2 infection was 99.5% (95% CI, 97.0 to 100.0%) at ≥14 days post-PCR confirmation. Overall specificity (n = 10,453) was 99.80% (95% CI, 99.69 to 99.88%). Only 4/792 samples containing potential cross-reacting analytes were reactive with the Elecsys Anti-SARS-CoV-2 immunoassay, resulting in an overall specificity in this cohort of 99.5% (95% CI, 98.6 to 99.9%). Positive, negative, and overall agreement (n = 46) between the Elecsys Anti-SARS-CoV-2 immunoassay and the pseudoneutralization assay were 86.4% (95% CI, 73.3 to 93.6%), 100% (95% CI, 34.2 to 100%), and 87.0% (95% CI, 74.3 to 93.9%), respectively. The Elecsys Anti-SARS-CoV-2 immunoassay demonstrated high sensitivity (99.5% at ≥14 days post-PCR confirmation) and specificity (99.80%), supporting its use as a tool for identification of past SARS-CoV-2 infection, including use in populations with low disease prevalence.

Clausal Density Between Ages 4 and 9 Years for the Edmonton Narrative Norms Instrument: Reference Data and Psychometric Properties

2020 ◽  
pp. 1-15
Author(s):  
Ling-Yu Guo ◽  
Phyllis Schneider ◽  
William Harrison
Keyword(s):  
Diagnostic Accuracy ◽  
Psychometric Properties ◽  
Language Impairment ◽  
Reference Data ◽  
Reliability And Validity ◽  
Correlation Coefficients ◽  
Criterion Validity ◽  
Likelihood Ratios ◽  
Generation Task ◽  
Sensitivity Specificity

Purpose This study provided reference data and examined psychometric properties for clausal density (CD; i.e., number of clauses per utterance) in children between ages 4 and 9 years from the database of the Edmonton Narrative Norms Instrument (ENNI). Method Participants in the ENNI database included 300 children with typical language (TL) and 77 children with language impairment (LI) between the ages of 4;0 (years;months) and 9;11. Narrative samples were collected using a story generation task, in which children were asked to tell stories based on six picture sequences. CD was computed from the narrative samples. The split-half reliability, concurrent criterion validity, and diagnostic accuracy were evaluated for CD by age. Results CD scores increased significantly between ages 4 and 9 years in children with TL and those with LI. Children with TL produced higher CD scores than those with LI at each age level. In addition, the correlation coefficients for the split-half reliability and concurrent criterion validity of CD scores were all significant at each age level, with the magnitude ranging from small to large. The diagnostic accuracy of CD scores, as revealed by sensitivity, specificity, and likelihood ratios, was poor. Conclusions The finding on diagnostic accuracy did not support the use of CD for identifying children with LI between ages 4 and 9 years. However, given the attested reliability and validity for CD, reference data of CD from the ENNI database can be used for evaluating children's difficulties with complex syntax and monitoring their change over time. Supplemental Material https://doi.org/10.23641/asha.13172129

Rate of Absorption of Water from Stomach and Small Bowel of Human Beings

1954 ◽  
Vol 27 (5) ◽  
pp. 565-577 ◽  
Author(s):  
John F. Scholer ◽  
Charles F. Code
Keyword(s):  
Small Bowel ◽  
Human Beings ◽  
Rate Of Absorption

Aortic arch calcification is strongly associated with coronary artery calcification

VASA ◽  
2015 ◽  
Vol 44 (2) ◽  
pp. 106-114 ◽  
Author(s):  
Adem Adar ◽  
Hakan Erkan ◽  
Tayyar Gokdeniz ◽  
Aysegul Karadeniz ◽  
Ismail G. Cavusoglu ◽  
...  
Keyword(s):  
Coronary Artery ◽  
High Risk ◽  
Aortic Arch ◽  
Chest Radiography ◽  
Coronary Artery Calcification ◽  
Independent Predictor ◽  
Study Group ◽  
Discriminative Performance ◽  
Sensitivity Specificity ◽  
Aortic Arch Calcification

Background: We aimed to investigate the association between aortic arch and coronary artery calcification (CAC). We postulated that low‐ and high‐risk CAC scores could be predicted with the evaluation of standard chest radiography for aortic arch calcification (AAC). Patients and methods: Consecutive patients who were referred for a multidetector computerized tomography (MDCT) examination were enrolled prospectively. All patients were scanned using a commercially available 64‐slice MDCT scanner for the evaluation of CAC score. A four‐point grading scale (0, 1, 2 and 3) was used to evaluate AAC on the standard posterior‐anterior chest radiography images. Results: The study group consisted of 248 patients. Median age of the study group was 52 (IQR: 10) years, and 165 (67 %) were male. AAC grades (r = 0.676, p < 0.0001) and age (r = 0.518, p < 0.0001) were significantly and positively correlated with CAC score. Presence of AAC was independently associated with the presence of CAC (OR: 11.20, 95 % CI 4.25 to 29.52). An AAC grade of ≥ 2 was the strongest independent predictor of a high‐risk CAC score (OR: 27.42, 95 % CI 6.09 to 123.52). Receiver operating characteristics curve analysis yielded a strong predictive ability of AAC grades for a CAC score of ≥ 100 (AUC = 0.892, P < 0.0001), and ≥ 400 (AUC = 0.894, P < 0.0001). Absence of AAC had a sensitivity, specificity and accuracy of 90 %, 84 % and 89 %, respectively, for a CAC score of < 100. An AAC grade of ≥ 2 predicted a CAC score of ≥400 with a sensitivity, specificity and accuracy of 68 %, 98 % and 95 %, respectively. Conclusions: AAC is a strong and independent predictor of CAC. The discriminative performance of AAC is high in detecting patients with low‐ and high‐risk CAC scores.

Comparison of Rheumatological Diagnoses by a Bayesian Program and by Physicians

1991 ◽  
Vol 30 (03) ◽  
pp. 187-193 ◽  
Author(s):  
H. J. Moens ◽  
J. K. van der Korst
Keyword(s):  
Receiver Operating Characteristics ◽  
Bayesian Decision ◽  
Operating Characteristics ◽  
Likelihood Ratios ◽  
Improve Performance ◽  
Mathematical Basis ◽  
Human Expert ◽  
Test Population ◽  
Sensitivity Specificity ◽  
Diagnostic Outcome

AbstractA Bayesian decision support system was developed for the diagnosis of rheumatic disorders. Knowledge in this system is represented as evidential weights of findings. Simple weights were calculated as the logarithm of likelihood ratios on the basis of 1,000 consecutive patients from a rheumatological clinic. The effect of various methods to improve performance of the system by modification of the weights was studied. Three methods had a mathematical basis; a fourth consisted of weights adapted by a human expert, which allowed inclusion of diagnostic rules such as defined in widely accepted criteria sets. The system’s performance was measured in a test population of 570 different cases from the same clinic and compared with predictions of diagnostic outcome made by rheumatologists. The weights from a human expert gave optimal results (sensitivity 65% and specificity 96%), that were close to the physicians’ predictions (sensitivity 64% and specificity 98%). The methods to measure the performance of the various models used in this study emphasize sensitivity, specificity and the use of receiver operating characteristics.

TO SEPARATELY ASSESS THE DIAGNOSTIC POTENTIAL OF TVS & MRI IN THE TERMS OF SENSITIVITY AND SPECIFICITY BY CORRELATING THE IMAGING FINDINGS WITH HISTOPATHOLOGY

2020 ◽  
Vol 4 (6) ◽  
Author(s):  
Suraj Mathur
Keyword(s):  
Transvaginal Ultrasound ◽  
High Sensitivity ◽  
Imaging Evaluation ◽  
Medical College ◽  
Conventional Mri ◽  
Diagnostic Potential ◽  
Adc Mapping ◽  
Malignant Lesions ◽  
Sensitivity Specificity

This prospective study was done in the Department of Radio diagnosis Govt. Medical College, Kozhikode. A total of 65 patients who were referred to our department with clinical suspicion of endometrial lesions and incidentally detected endometrial lesions on ultrasonography underwent transvaginal ultrasound and subsequent Imaging evaluation of pelvis MRI has very high sensitivity (95%) and specificity (98%) and is almost as accurate (97%) as histopathology in differentiating benign from malignant lesions. Addition of DWI with ADC mapping to conventional MRI increases its accuracy even more. However there is inherent limitation to MRI in detecting carcinoma in situ and micrometastasis. Keywords: TVS, MRI, Sensitivity, Specificity, Histopathology.

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