scholarly journals Strontium as a Marker for Intestinal Calcium Absorption: The Stimulatory Effect of Calcitriol

2000 ◽  
Vol 46 (2) ◽  
pp. 248-251 ◽  
Author(s):  
Marieke Dijkgraaf-ten Bolscher ◽  
J Coen Netelenbos ◽  
Rob Barto ◽  
Wim J F van der Vijgh
Keyword(s):  
Calcium Absorption ◽  
Intestinal Calcium Absorption ◽  
Clinical Test ◽  
Time Curve ◽  
Blood Samples ◽  
Healthy Men ◽  
The Third ◽  
Healthy Humans ◽  
Concentration Time ◽  
Better Than

Abstract Background: Intestinal strontium absorption is becoming accepted as a clinical and diagnostic tool for assessing intestinal calcium absorption in humans. However, little is known about whether intestinal strontium absorption, like that of calcium, is stimulated by calcitriol in healthy humans. Methods: The effect of calcitriol on intestinal strontium absorption was measured in eight healthy men, ages 20–60 years. Before administration of calcitriol, two tests were performed with an interval of 10 days for calculating the within-subject variation (SER). Before the third test, 0.5 μg of calcitriol was given twice daily for 3 days. In each test, the fractional strontium absorption (Fc240) and the area under the concentration-time curve (AUC0–240) 4 h after an oral strontium load of 2.5 mmol were calculated. Results: The within-subject SER of Fc240 and AUC0–240 was 1.7 ± 0.7 and 0.83 ± 0.1, respectively. The stimulatory effect of calcitriol on Fc240 and AUC0–240 was 35% (21.8 ± 2.0 to 28.8 ± 2.4; P = 0.003) and 61% (8.97 ± 0.97 to 14.4 ± 1.3 mmol · L−1 · min; P = 0.001), respectively. Conclusions: Although the reproducibility of AUC0–240 and its sensitivity to calcitriol were better than those of Fc240, the Fc240 of strontium is preferred for a clinical test because of its simplicity, requiring only two instead of five blood samples.

Intestinal strontium absorption: from bioavailability to validation of a simple test representative for intestinal calcium absorption

1995 ◽  
Vol 41 (10) ◽  
pp. 1446-1450 ◽  
Author(s):  
A J Sips ◽  
W J van der Vijgh ◽  
R Barto ◽  
J C Netelenbos
Keyword(s):  
Calcium Absorption ◽  
Intestinal Calcium Absorption ◽  
Absolute Bioavailability ◽  
Clinical Test ◽  
Strontium Chloride ◽  
Simple Test ◽  
Intraindividual Variation ◽  
Time Curve ◽  
Test Variable ◽  
The Absolute

Abstract Calcium absorption tests have rarely been validated for being representative for absolute bioavailability (true absorption) or for intraindividual variation. Therefore, we investigated the reproducibility of the absolute bioavailability of strontium chloride, a marker for intestinal calcium absorption, in healthy male volunteers (n = 8) by measuring the area under the plasma strontium concentration-time curve after oral and intravenous administration of strontium. Subsequently, we selected a simple test variable as being representative of absolute bioavailability. The mean absolute bioavailability (+/- SD) was 25% +/- 7%. The best test variable appeared to be the fractional absorption at 240 min (Fc240) after oral intake, which demonstrated the highest correlation with absolute bioavailability (r = 0.66). The intraindividual variations of the data for this variable and for the absolute bioavailability are similar to those described for various absorption tests based on the use of calcium isotopes. Thus, the Fc240 of strontium offers the potential of a simple clinical test for use as a measure of intestinal calcium absorption and its modulation.

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

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%.

scholarly journals Pharmacokinetic Interaction between Pyronaridine-Artesunate and Metoprolol

2014 ◽  
Vol 58 (10) ◽  
pp. 5900-5908 ◽  
Author(s):  
Carrie A. Morris ◽  
Rolf Pokorny ◽  
Luis Lopez-Lazaro ◽  
Robert M. Miller ◽  
Sarah Arbe-Barnes ◽  
...  
Keyword(s):  
Healthy Adult ◽  
Pharmacokinetic Interaction ◽  
Liver Function Tests ◽  
Pharmacokinetic Parameters ◽  
Metoprolol Tartrate ◽  
Time Curve ◽  
The Third ◽  
Concentration Time ◽  
Second Period ◽  
Quantifiable Concentration

ABSTRACTThe objectives of this study were to characterize any drug-drug interaction between the antimalarial Pyramax (pyronaridine-artesunate [PA]) and the CYP2D6 probe substrate metoprolol and to assess the safety of 60-day or 90-day PA redosing, particularly with regard to liver biochemistry parameters. Healthy adult subjects were randomized to arm A (n= 26) or arm B (n= 30), with the arm A subjects administered 100 mg metoprolol tartrate in the first period, 100 mg metoprolol tartrate with the third of three daily doses of PA in the second period, and three daily doses of PA alone in the 90-day redosing period. The arm B subjects received the three-day PA regimen in the first period, with redosing of the regimen after 60 days in the second period. The noncompartmental pharmacokinetic parameters were computed for metoprolol, its metabolite alpha-hydroxymetoprolol, and pyronaridine. The coadministration of metoprolol and PA was associated with an average 47.93% (90% confidence interval [CI], 30.52, 67.66) increase in the maximum concentration of metoprolol and a 25.60% (90% CI, 15.78, 36.25) increase in the metoprolol area under the concentration-time curve from time zero to the last quantifiable concentration obtained (AUC0-t); these increases most likely resulted from pyronaridine-mediated CYP2D6 inhibition. No interaction effect of metoprolol with pyronaridine was apparent. Following dosing with PA, some subjects experienced rises in liver function tests above the upper limit of normal during the first few days following PA administration. All such elevations resolved typically within 10 days, and up to 30 days at most. In subjects who were redosed, the incidences of alanine aminotransferase (ALT) or aspartate transaminase (AST) level elevations were similar on the first and second administrations, with no marked difference between the 60-day and 90-day redosing.

scholarly journals Early Postpartum Pharmacokinetics of Lopinavir Initiated Intrapartum in Thai Women

2009 ◽  
Vol 53 (5) ◽  
pp. 2189-2191 ◽  
Author(s):  
Tim R. Cressey ◽  
Russell Van Dyke ◽  
Gonzague Jourdain ◽  
Thanyawee Puthanakit ◽  
Anuvat Roongpisuthipong ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Third Trimester ◽  
Serious Adverse Events ◽  
Time Curve ◽  
Thai Women ◽  
The Third ◽  
Early Postpartum Period ◽  
Concentration Time ◽  
Early Postpartum ◽  
Immunodeficiency Virus

ABSTRACT Lopinavir (LPV) exposure is reduced during the third trimester of pregnancy. We report the pharmacokinetics of standard LPV-ritonavir dosing (400/100 mg twice daily) in the immediate and early postpartum period when initiated during labor. In 16 human immunodeficiency virus-infected Thai women, the median (range) LPV area under the concentration-time curve and maximum and minimum concentrations in plasma were 99.7 (66.1 to 180.5) μg·h/ml, 11.2 (8.0 to 17.5) μg/ml, and 4.6 (1.7 to 12.5) μg/ml, respectively, at 41 (12 to 74) h after delivery. All of the women attained adequate LPV levels through 30 days postpartum. No serious adverse events were reported.

scholarly journals Improved Oral Bioavailability of Lopinavir in Melt-Extruded Tablet Formulation Reduces Impact of Third Trimester on Lopinavir Plasma Concentrations

2011 ◽  
Vol 56 (2) ◽  
pp. 816-824 ◽  
Author(s):  
L. J. Else ◽  
M. Douglas ◽  
L. Dickinson ◽  
D. J. Back ◽  
S. H. Khoo ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Plasma Concentrations ◽  
Undetectable Viral Load ◽  
Pharmacokinetic Data ◽  
Third Trimester ◽  
Time Curve ◽  
The Third ◽  
Concentration Time ◽  
Liquid Chromatography Tandem Mass ◽  
In Pregnancy

ABSTRACTLopinavir exposure was reduced during the third trimester in pregnant women receiving standard dosing of the soft-gel capsule (SGC; 400/100 mg twice daily [b.i.d.]). Pharmacokinetic data on the lopinavir tablet in pregnancy are limited. On the basis of the tablet's improved bioavailability, standard dosing (400/100 mg b.i.d.) may provide adequate lopinavir exposure in pregnancy without a need for dose adjustment. Here we compared the total and unbound lopinavir pharmacokinetics throughout pregnancy in the second and third trimesters in HIV-infected women receiving standard dosing of the lopinavir SGC or tablet. Postpartum sampling was also performed in patients continuing therapy postdelivery. Blood samples were collected at 0 to 12 h postdosing, and lopinavir concentrations were determined by high-pressure liquid chromatography-tandem mass spectrometry. Nineteen patients were included: 8 received the SGC (cohort 1) and 11 received the tablet (cohort 2). Total lopinavir exposures in the third trimester were lower than those in the second trimester (35 and 28% for cohorts 1 and 2, respectively) and postpartum (35% for cohort 2). In the third trimester, the area under the concentration-time curve (AUC) from 0 to 12 h (AUC0–12) and maximum concentration were ∼15% and 25% higher, respectively, for the lopinavir tablet than the SGC. One SGC patient had lopinavir concentrations of <1,000 ng/ml; all patients on the tablet had concentrations of >1,000 ng/ml. In cohort 2, the percentage of the AUC that was unbound was higher (nonsignificantly) in the second (1.28%) and third (1.18%) trimesters than postpartum (1.01%). Seventeen of 19 patients had an undetectable viral load at delivery. There were no HIV transmissions. Although lopinavir (tablet) exposures were reduced during the third trimester, the higher total and unbound concentrations achieved in women receiving the tablet than in women receiving the SGC suggest that the tablet's improved oral bioavailability may partly compensate for the reduction in lopinavir exposure during the later stages of pregnancy.

Effect of Terbinafine on Theophylline Pharmacokinetics in Healthy Volunteers

1998 ◽  
Vol 42 (3) ◽  
pp. 695-697 ◽  
Author(s):  
Eric F. Trépanier ◽  
Anne N. Nafziger ◽  
Guy W. Amsden
Keyword(s):  
Healthy Volunteers ◽  
Multiple Dose ◽  
Treatment Phase ◽  
Pharmacokinetic Parameters ◽  
Noncompartmental Analysis ◽  
Open Label ◽  
Time Curve ◽  
Blood Samples ◽  
Concentration Time ◽  
Randomized Crossover Study

ABSTRACT Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) with and without multiple-dose terbinafine, and 11 blood samples were collected over 24 h. The study phases were separated by a 4-week washout period. Theophylline serum data were modeled via noncompartmental analysis. When the control phase (i.e., no terbinafine) was compared to the treatment phase (terbinafine), theophylline exposure (the area under the serum concentration-time curve from time zero to infinity) increased by 16% (P= 0.03), oral clearance decreased by 14% (P = 0.04), and half-life increased by 24% (P = 0.002). No significant changes in other theophylline pharmacokinetic parameters were evident.

Intestinal calcium absorption during hyperinsulinemic euglycemic glucose clamp in healthy humans

1990 ◽  
Vol 46 (2) ◽  
pp. 73-79 ◽  
Author(s):  
Gerhard Rümenapf ◽  
Johanna Schmidtler ◽  
Paul Otto Schwille
Keyword(s):  
Calcium Absorption ◽  
Intestinal Calcium Absorption ◽  
Glucose Clamp ◽  
Healthy Humans

A Developmental Study of Intonation Recognition

1968 ◽  
Vol 11 (4) ◽  
pp. 825-832 ◽  
Author(s):  
Marilyn M. Corlew
Keyword(s):  
Significant Interaction ◽  
Multiple Choice ◽  
Semantic Content ◽  
First Grade ◽  
Choice Test ◽  
Developmental Study ◽  
Multiple Choice Test ◽  
The Third ◽  
Matching Test ◽  
Better Than

Two experiments investigated the information conveyed by intonation from speaker to listener. A multiple-choice test was devised to test the ability of 48 adults to recognize and label intonation when it was separated from all other meaning. Nine intonation contours whose labels were most agreed upon by adults were each matched with two English sentences (one with appropriate and one with inappropriate intonation and semantic content) to make a matching-test for children. The matching-test was tape-recorded and given to children in the first, third, and fifth grades (32 subjects in each grade). The first-grade children matched the intonations with significantly greater agreement than chance; but they agreed upon significantly fewer sentences than either the third or fifth graders. Some intonation contours were matched with significantly greater frequency than others. The performance of the girls was better than that of the boys on an impatient question and a simple command which indicates that there was a significant interaction between sex and intonation.

Using Connectionist Modules for Decision Support

1990 ◽  
Vol 29 (03) ◽  
pp. 167-181 ◽  
Author(s):  
G. Hripcsak
Keyword(s):  
Decision Support ◽  
Standard Deviation ◽  
Confidence Interval ◽  
Posterior Probability ◽  
Back Propagation ◽  
Connectionist Model ◽  
Test Set ◽  
The Third ◽  
Independent Test ◽  
Better Than

AbstractA connectionist model for decision support was constructed out of several back-propagation modules. Manifestations serve as input to the model; they may be real-valued, and the confidence in their measurement may be specified. The model produces as its output the posterior probability of disease. The model was trained on 1,000 cases taken from a simulated underlying population with three conditionally independent manifestations. The first manifestation had a linear relationship between value and posterior probability of disease, the second had a stepped relationship, and the third was normally distributed. An independent test set of 30,000 cases showed that the model was better able to estimate the posterior probability of disease (the standard deviation of residuals was 0.046, with a 95% confidence interval of 0.046-0.047) than a model constructed using logistic regression (with a standard deviation of residuals of 0.062, with a 95% confidence interval of 0.062-0.063). The model fitted the normal and stepped manifestations better than the linear one. It accommodated intermediate levels of confidence well.

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