Method for evaluating the human bioequivalence of acarbose based on pharmacodynamic parameters

Objective To explore a method for evaluating the bioequivalence of acarbose based on pharmacodynamic parameters using a single-dose, randomized-sequence, three-way crossover study of acarbose test (T) and reference (R) formulations. Methods Baseline-adjusted, pre-dose value deduction, and direct comparison methods were used to evaluate the geometric T/R ratios and 90% confidence intervals (CIs) of the ln-transformed pharmacodynamic parameters to identify the most suitable evaluation system. Twelve participants were randomly divided into three groups to receive treatment in the following sequences: TRR, RTR, and RRT, each including a 7-day washout period between treatment periods. The serum glucose concentration (baseline) was determined. Pharmacodynamic parameters, including the maximum reduction in serum glucose concentrations (ΔCSG,max) and difference of the AUC of glucose between before and after acarbose exposure (ΔAUEC), were tested. Results Using the direct comparison method, the geometric mean ratios of CSG,max, AUEC(0-2h), and AUEC(0-4h) were 94.13%, 97.82% and 99.76%, respectively. The 90% CIs of the geometric T/R ratios for CSG,max, AUEC(0-2h), and AUEC(0-4h) all fell between 80% and 125%. Conversely, ΔCSG,max and ΔAUEC(0-4h) were less reliable measures of acarbose bioequivalence. Conclusions Pre-dose value deduction and direct comparison methods can be initially considered suitable for assessing acarbose bioequivalence.

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Quadrivalent Meningococcal Vaccination of Adults: Phase III Comparison of an Investigational Conjugate Vaccine, MenACWY-CRM, with the Licensed Vaccine, Menactra

Clinical and Vaccine Immunology ◽

10.1128/cvi.00207-09 ◽

2009 ◽

Vol 16 (12) ◽

pp. 1810-1815 ◽

Cited By ~ 62

Author(s):

Keith S. Reisinger ◽

Roger Baxter ◽

Stanley L. Block ◽

Jina Shah ◽

Lisa Bedell ◽

...

Keyword(s):

Single Dose ◽

Conjugate Vaccine ◽

Geometric Mean ◽

Case Fatality ◽

The United States ◽

Phase Iii ◽

Serum Samples ◽

Serious Adverse Event ◽

Specific Serum ◽

To Receive

ABSTRACT Neisseria meningitidis is a leading cause of bacterial meningitis in the United States, with the highest case fatality rates reported for individuals ≥15 years of age. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM197 conjugate vaccine, MenACWY-CRM, to those of the licensed meningococcal conjugate vaccine, Menactra, when administered to healthy adults. In this phase III multicenter study, 1,359 adults 19 to 55 years of age were randomly assigned to one of four groups (1:1:1:1 ratio) to receive a single dose of one of three lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained at baseline and 1 month postvaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers following vaccination with MenACWY-CRM and Menactra were compared in noninferiority and prespecified superiority analyses. Reactogenicity was similar in the MenACWY-CRM and Menactra groups, and neither vaccine was associated with a serious adverse event. When compared with Menactra, MenACWY-CRM met the superiority criteria for the proportions of recipients achieving a seroresponse against serogroups C, W-135, and Y and the proportion of subjects achieving postvaccination titers of ≥1:8 for serogroups C and Y. MenACWY-CRM's immunogenicity was statistically noninferior (the lower limit of the two-sided 95% confidence interval was more than −10%) to that of Menactra for all four serogroups, with the postvaccination hSBA geometric mean titers being consistently higher for MenACWY-CRM than for Menactra. MenACWY-CRM is well tolerated in adults 19 to 55 years of age, with immune responses to each of the serogroups noninferior and, in some cases, statistically superior to those to Menactra.

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The Efficacy of Single-Dose versus Double-Dose Praziquantel Treatments onSchistosoma mansoniInfections: Its Implication on Undernutrition and Anaemia among Primary Schoolchildren in Two On-Shore Communities, Northwestern Tanzania

BioMed Research International ◽

10.1155/2017/7035025 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 12

Author(s):

David Z. Munisi ◽

Joram Buza ◽

Emmanuel A. Mpolya ◽

Teckla Angelo ◽

Safari M. Kinung’hi

Keyword(s):

Single Dose ◽

Geometric Mean ◽

Reduction Rate ◽

Repeated Dose ◽

Cure Rate ◽

Treatment Regimens ◽

Northwestern Tanzania ◽

Primary Schoolchildren ◽

The Mean ◽

To Receive

Administering more than one treatment may increase Praziquantel cure and egg reduction rates, thereby hastening achievement of schistosomiasis transmission control. A total of 431S. mansoni-infected schoolchildren were randomized to receive either a single or repeated 40 mg/kg Praziquantel dose. Heights, weights, and haemoglobin levels were determined using a stadiometer, weighing scale, and HemoCue, respectively. At 8 weeks, cure rate was higher on repeated dose (93.10%) compared to single dose (68.68%) (p<0.001). The egg reduction rate was higher on repeated dose (97.54%) compared to single dose (87.27%) (p=0.0062). Geometric mean egg intensity was lower among those on repeated dose (1.30 epg) compared to single dose (3.18 epg) (p=0.036) but not at 5 (p>0.05) and 8 (p>0.05) months with no difference in reinfection rate. No difference in the prevalence of stunting was observed between the two treatment regimens (p>0.05) at 8 months, but there was an increase in the prevalence of wasting among those on repeated dose (p<0.001). There was an increase in the mean haemoglobin levels at 8 months with no difference between the two arms (p>0.05). To achieve reduction of transmission intensity and disease control in highly endemic areas, repeated treatments alone may not be sufficient. This trial was registered withPACTR201601001416338.

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The effect of retinyl palmitate added to iron-fortified maize porridge on erythrocyte incorporation of iron in African children with vitamin A deficiency

British Journal Of Nutrition ◽

10.1079/bjn2003914 ◽

2003 ◽

Vol 90 (2) ◽

pp. 337-343 ◽

Cited By ~ 15

Author(s):

Lena Davidsson ◽

Pierre Adou ◽

Christophe Zeder ◽

Thomas Walczyk ◽

Richard Hurrell

Keyword(s):

Single Dose ◽

Vitamin A ◽

Test Meal ◽

Vitamin A Deficiency ◽

Geometric Mean ◽

Retinyl Palmitate ◽

Dietary Vitamin ◽

Vitamin A Supplementation ◽

Vitamin A Status ◽

Before And After

Retinyl palmitate added to Fe-fortified maize bread has been reported to enhance Fe absorption in adult Venezuelan subjects but not in Western Europeans. It is not known to what extent these results were influenced by differences in vitamin A status of the study subjects. The objective of the present study was to evaluate the influence of retinyl palmitate added to Fe-fortified maize porridge on erythrocyte incorporation of Fe in children with vitamin A deficiency, before and after vitamin A supplementation. Erythrocyte incorporation of Fe-stable isotopes was measured 14 d after intake of maize porridge (2·0 mg Fe added as ferrous sulfate) with and without added retinyl palmitate (3·5 μmol; 3300 IU). The study was repeated 3 weeks after vitamin A supplementation (intake of a single dose of 210 μmol retinyl palmitate; ‘vitamin A capsule’). Vitamin A status was evaluated by the modified relative dose–response (MRDR) technique. Retinyl palmitate added to the test meal reduced the geometric mean erythrocyte incorporation of Fe at baseline from 4·0 to 2·6 % (P=0·008, n 13; paired t test). At 3 weeks after vitamin A supplementation, geometric mean erythrocyte incorporation was 1·9 and 2·3 % respectively from the test meal with and without added retinyl palmitate (P=0·283). Mean dehydroretinol:retinol molar ratios were 0·156 and 0·125 before and after intake of the single dose of 210 μmol retinyl palmitate; ‘vitamin A capsule’ (P=0·15). In conclusion, retinyl palmitate added to the labelled test meals significantly decreased erythrocyte incorporation of Fe in children with vitamin A deficiency at baseline but had no statistically significant effect 3 weeks after vitamin A supplementation. The difference in response to retinyl palmitate added to Fe-fortified maize porridge on erythrocyte incorporation of Fe before and after intake of the vitamin A capsule indicates, indirectly, changes in vitamin A status not measurable by the MRDR technique. The lack of conclusive data on the effect of retinyl palmitate on Fe absorption indicates the complexity of the interactions between vitamin A status, dietary vitamin A and Fe metabolism.

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Bioequivalence Study of Rivastigmine 6 mg Capsules (Single Dose) in Healthy Volunteers

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317517712890 ◽

2017 ◽

Vol 32 (6) ◽

pp. 360-366

Author(s):

Dhiraj Abhyankar ◽

Ashish Shedage ◽

Milind Gole ◽

Preeti Raut

Keyword(s):

Single Dose ◽

Standard Deviation ◽

Geometric Mean ◽

Bioequivalence Study ◽

Open Label ◽

Time Curve ◽

Healthy Men ◽

Time Zero ◽

Concentration Time ◽

To Receive

Objective: To assess the bioequivalence of generic formulation of rivastigmine (test) and Exelon (reference). Methods: This randomized, open-label, 2-period, single-dose, 2-treatment, 2-sequence, crossover study was conducted in 40 healthy men under fed condition. Participants were randomized to receive a single dose of Exelon or rivastigmine capsule. Results: A total of 31 participants completed the study. Area under the concentration–time curve from time zero to time t (AUC0- t) and area under the concentration–time curve from time zero to infinity (AUC0-∞) for Exelon (mean [standard deviation], h·ng/mL) were 126.40 (56.95) and 129.46 (59.94), respectively, while they were 122.73 (43.46) and 125.08 (45.39) for rivastigmine. Geometric mean ratios of rivastigmine/Exelon were 99.17% for AUC0- t, 98.81% for AUC0-∞, and 105% for maximum observed plasma concentration ( Cmax). The 90% confidence intervals (CIs) were 94.14% to 104.46%, 93.77% to 104.12%, and 93.08% to 118.44%, respectively. Both formulations were well tolerated. Conclusion: The generic and reference formulations were bioequivalent, as the 90% CIs for Cmax, AUC0- t, and AUC0-∞ were within the range of 80% to 125%.

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Immunogenicity of a Reduced Schedule of Meningococcal Group C Conjugate Vaccine Given Concomitantly with the Prevenar and Pediacel Vaccines in Healthy Infants in the United Kingdom

Clinical and Vaccine Immunology ◽

10.1128/cvi.00420-08 ◽

2008 ◽

Vol 16 (2) ◽

pp. 194-199 ◽

Cited By ~ 52

Author(s):

Jo Southern ◽

Ray Borrow ◽

Nick Andrews ◽

Rhonwen Morris ◽

Pauline Waight ◽

...

Keyword(s):

Single Dose ◽

Conjugate Vaccine ◽

Geometric Mean ◽

Tetanus Antitoxin ◽

The United Kingdom ◽

Healthy Infants ◽

Meningococcal Group ◽

Bactericidal Antibody ◽

Polyribosylribitol Phosphate ◽

To Receive

ABSTRACT This study investigated the use of two doses of three different meningococcal group C conjugate (MCC) vaccines when given for primary immunization with a seven-valent pneumococcal conjugate vaccine (PCV7) and Pediacel, a combination product containing five acellular pertussis components, diphtheria and tetanus toxoids, Haemophilus influenzae type b (Hib) conjugate, and inactivated-poliovirus vaccine. The immune response after a single dose of MCC is also presented. Infants were randomized to receive two doses of one of the MCC vaccines and PCV7 at 2 and 3 months or at 2 and 4 months of age. Meningococcal group C serum bactericidal antibody (SBA) geometric mean titers, Hib-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) geometric mean concentrations (GMCs), and diphtheria and tetanus antitoxin GMCs, together with the proportions of infants achieving putative protective levels, were determined. A total of 393 infants were recruited. Following the first dose of NeisVac-C (MCC conjugated to tetanus toxoid), 97% of infants achieved protective levels (SBA titer of ≥8), compared with 80% and 53%, respectively, for Menjugate and Meningitec (both of which are conjugated to CRM197). SBA responses to MCC vaccines were not significantly different when administered at 2 and 3 or 2 and 4 months of age. Following two doses of each MCC, 98 to 100% of infants achieved protective levels. Both PRP IgG and tetanus responses were significantly enhanced when Pediacel was coadministered with NeisVac-C. This study demonstrates that NeisVac-C and Menjugate generate good immunogenicity after the first dose at 2 months of age when coadministered with PCV7 and Pediacel and merit further investigation in single-dose priming strategies.

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Loss of the preconditioning effect of rosuvastatin during sustained therapy: a human in vivo study

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00083.2011 ◽

2012 ◽

Vol 302 (1) ◽

pp. H153-H158 ◽

Cited By ~ 10

Author(s):

Andrew Liuni ◽

Mary Clare Luca ◽

Tommaso Gori ◽

John D. Parker

Keyword(s):

Single Dose ◽

Treatment Group ◽

Group Interaction ◽

Acute Administration ◽

Reductase Inhibitors ◽

Before And After ◽

Hmg Coa Reductase Inhibitors ◽

Coa Reductase ◽

To Receive ◽

Administration Protocol

Studies have demonstrated that the acute administration of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has protective effects in the setting of ischemia-reperfusion (IR). Previously, we demonstrated that a single dose of rosuvastatin prevented IR-induced endothelial dysfunction in humans through a cyclooxygenase-2-dependent mechanism. Whether the chronic administration of HMG-CoA reductase inhibitors provides similar protection remains controversial and is unknown in humans. Eighteen male volunteers were randomized to receive a single dose of rosuvastatin (20 mg) or placebo. Twenty-four hours later, endothelium-dependent, radial artery flow-mediated dilation (FMD) was measured before and after IR (15 min of upper arm ischemia followed by 15 min of reperfusion). In a separate protocol, 30 healthy volunteers were randomized in a double-blind fashion to receive oral rosuvastatin (20 mg/day) and placebo, rosuvastatin, and celecoxib (100 mg bid) or placebo alone, all for 21 days. Twenty-four hours after the final administration of study medication, FMD was measured before and after IR. Pre-IR FMD was similar between groups in both protocols. In the acute administration protocol, rosuvastatin significantly prevented the blunting of FMD associated with IR (FMD pre-IR: 8.4 ± 1.3%; post-IR: 6.2 ± 1.3%; P = 0.01 ANOVA, treatment group interaction). In the daily administration protocol, IR significantly blunted FMD in the placebo group (FMD pre-IR: 7.5 ± 0.9%; post-IR: 3.3 ± 0.7%; P < 0.001). Chronic treatment with rosuvastatin did not modify this ischemic injury (FMD pre-IR: 6.9 ± 0.4%; post-IR: 1.6 ± 1.0%; P < 0.001; P = NS ANOVA, treatment group interaction). Similarly, FMD responses post-IR in volunteers receiving rosuvastatin and celecoxib did not significantly differ from placebo (FMD pre-IR: 8.3 ± 0.9%; post-IR: 2.1 ± 0.8%; P < 0.001; P = NS ANOVA, treatment group interaction). In contrast to acute administration, chronic rosuvastatin does not prevent the development of IR-induced endothelial dysfunction in normal humans.

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DMSA-scintigraphy in paediatrics: Is the evaluation of the geometric mean necessary for the calculation of the differential renal function?

Nuklearmedizin ◽

10.1055/s-0038-1625921 ◽

2001 ◽

Vol 40 (04) ◽

pp. 107-110 ◽

Cited By ~ 1

Author(s):

B. Roßmüller ◽

S. Alalp ◽

S. Fischer ◽

S. Dresel ◽

K. Hahn ◽

...

Keyword(s):

Renal Function ◽

Geometric Mean ◽

Region Of Interest ◽

Posterior View ◽

Renal Abnormality ◽

Anterior View ◽

Differential Renal Function ◽

The Mean ◽

The Right ◽

To Receive

SummaryFor assessment of differential renal function (PF) by means of static renal scintigraphy with Tc-99m-dimer-captosuccinic acid (DMSA) the calculation of the geometric mean of counts from the anterior and posterior view is recommended. Aim of this retrospective study was to find out, if the anterior view is necessary to receive an accurate differential renal function by calculating the geometric mean compared to calculating PF using the counts of the posterior view only. Methods: 164 DMSA-scans of 151 children (86 f, 65 m) aged 16 d to 16 a (4.7 ± 3.9 a) were reviewed. The scans were performed using a dual head gamma camera (Picker Prism 2000 XP, low energy ultra high resolution collimator, matrix 256 x 256,300 kcts/view, Zoom: 1.6-2.0). Background corrected values from both kidneys anterior and posterior were obtained. Using region of interest technique PF was calculated using the counts of the dorsal view and compared with the calculated geometric mean [SQR(Ctsdors x Ctsventr]. Results: The differential function of the right kidney was significantly less when compared to the calculation of the geometric mean (p<0.01). The mean difference between the PFgeom and the PFdors was 1.5 ± 1.4%. A difference > 5% (5.0-9.5%) was obtained in only 6/164 scans (3.7%). Three of 6 patients presented with an underestimated PFdors due to dystopic kidneys on the left side in 2 patients and on the right side in one patient. The other 3 patients with a difference >5% did not show any renal abnormality. Conclusion: The calculation of the PF from the posterior view only will give an underestimated value of the right kidney compared to the calculation of the geometric mean. This effect is not relevant for the calculation of the differntial renal function in orthotopic kidneys, so that in these cases the anterior view is not necesssary. However, geometric mean calculation to obtain reliable values for differential renal function should be applied in cases with an obvious anatomical abnormality.

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Grading Teachers: Race and Gender Differences in Low Evaluation Ratings and Teacher Employment Outcomes

American Educational Research Journal ◽

10.3102/0002831219835776 ◽

2019 ◽

Vol 56 (5) ◽

pp. 1800-1833 ◽

Cited By ~ 3

Author(s):

Steven Drake ◽

Amy Auletto ◽

Joshua M. Cowen

Keyword(s):

Charter Schools ◽

Evaluation System ◽

Employment Outcomes ◽

Teachers Of Color ◽

High Stakes ◽

Teacher Labor Market ◽

Race And Gender ◽

And Gender ◽

To Receive ◽

The Relationship

In July 2011, the State of Michigan adopted a broad set of teacher labor market reforms, including a high-stakes evaluation system designed in part to remove low-performing teachers. We examine the characteristics of teachers rated as “minimally effective” and “ineffective,” as well as their schools, and the relationship between low effectiveness ratings and later employment outcomes. Results suggest teachers of color across traditional and charter schools are more likely to receive low effectiveness ratings than their within-school peers. These low rating risks are higher for teachers of color working in comparatively White-faculty contexts. Male and novice teachers are also rated low more frequently, and important differences appear to exist in the usage of low ratings by traditional public and charter schools.

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Frühgeborene unter maschineller Beatmung: Immunmodulatorischer Effekt der präventiven Gabe von Azithromycin

Karger Kompass Pneumologie ◽

10.1159/000513487 ◽

2020 ◽

pp. 1-3

Author(s):

Maximilian Jorczyk

Keyword(s):

Very Low Birth Weight ◽

Controlled Trial ◽

Preterm Neonates ◽

Double Blind ◽

Mechanically Ventilated ◽

Before And After ◽

Anti Inflammatory ◽

To Receive ◽

Therapeutic Possibilities ◽

Inflammatory Effect

Introduction: Macrolides have anti-inflammatory and immunomodulatory properties that give this class of antibiotics a role that differs from its classical use as an antibiotic, which opens new therapeutic possibilities. Objective: The aim of this study was to evaluate the anti-inflammatory effect of azithromycin in preventing mechanical ventilation (MV)-induced lung injury in very-low-birth-weight preterm neonates. Methods: This is a randomized, double-blind, placebo-controlled trial of preterm neonates who received invasive MV within 72 h of birth. Patients were randomized to receive intravenous azithromycin (at a dose of 10/mg/kg/day for 5 days) or placebo (0.9% saline) within 12 h of the start of MV. Two blood samples were collected (before and after intervention) for measurement of interleukins (ILs) and PCR for Ureaplasma. Patients were followed up throughout the hospital stay for the outcomes of death and bronchopulmonary dysplasia defined as need for oxygen for a period of ≥28 days of life (registered at ClinicalTrials.gov, No. NCT03485703). Results: Forty patients were analyzed in the azithromycin group and 40 in the placebo group. Five days after the last dose, serum IL-2 and IL-8 levels dropped significantly in the azithromycin group. There was a significant reduction in the incidence of death and O2 dependency at 28 days/death in azithromycin-treated patients regardless of the detection of Ureaplasma in blood. Conclusions: Azithromycin has anti-inflammatory effects, with a decrease in cytokines after 5 days of use and a reduction in death and O2 dependency at 28 days/death in mechanically ventilated preterm neonates.

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Effect of Adherence to Physical Exercise on Cardiometabolic Profile in Postmenopausal Women

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18020656 ◽

2021 ◽

Vol 18 (2) ◽

pp. 656

Author(s):

Valentina Bucciarelli ◽

Francesco Bianco ◽

Francesco Mucedola ◽

Andrea Di Blasio ◽

Pascal Izzicupo ◽

...

Keyword(s):

Physical Exercise ◽

Diastolic Function ◽

Postmenopausal Women ◽

Serum Glucose ◽

Moderate Intensity ◽

Adherence Rate ◽

Before And After ◽

Estrogen Depletion ◽

The Impact ◽

Cardiometabolic Profile

Background: Menopause is associated with negative cardiovascular adaptations related to estrogen depletion, which could be counteracted by physical exercise (PhE). However, the impact of total adherence-rate (TA) to PhE and sedentary time (SedT) on cardiometabolic profile in this population has not been elucidated. Methods: For 13-weeks, 43 women (57.1 ± 4.7 years) participated in a 4-days-a-week moderate-intensity walking training. They underwent laboratory, anthropometric and echocardiographic assessment, before and after training (T0–T1). Spontaneous physical activity (PhA) was assessed with a portable multisensory device. The sample was divided according to TA to PhE program: <70% (n = 17) and ≥70% (n = 26). Results: TA ≥ 70% group experienced a significant T1 improvement of relative wall thickness (RWT), diastolic function, VO2max, cortisol, cortisol/dehydroandrostenedione-sulphate ratio and serum glucose. After adjusting for SedT and 10-min bouts of spontaneous moderate-to-vigorous PhA, TA ≥ 70% showed the most significant absolute change of RWT and diastolic function, body mass index, weight and cortisol. TA ≥ 70% was major predictor of RWT and cortisol improvement. Conclusions: In a group of untrained, postmenopausal women, a high TA to a 13-weeks aerobic PhE program confers a better improvement in cardiometabolic profile, regardless of SedT and PhA levels.

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