scholarly journals Optimal Sampling Strategies to Assess Inulin Clearance in Children by the Inulin Single-Injection Method

2003 ◽  
Vol 49 (7) ◽  
pp. 1170-1179 ◽  
Author(s):  
Lyonne K van Rossum ◽  
Ron A A Mathot ◽  
Karlien Cransberg ◽  
Arnold G Vulto
Keyword(s):  
Pediatric Patients ◽  
Bolus Injection ◽  
Single Injection ◽  
Inulin Clearance ◽  
Optimal Sampling ◽  
Sampling Strategies ◽  
Injection Method ◽  
Validation Set ◽  
Sampling Times ◽  
Single Bolus Injection

Abstract Background: Glomerular filtration rate in patients can be determined by estimating the plasma clearance of inulin with the single-injection method. In this method, a single bolus injection of inulin is administered and several blood samples are collected. For practical and convenient application of this method in children, it is important that a minimal number of samples are drawn. The aim of this study was to develop and validate sampling strategies with fewer samples for reliable prediction of inulin clearance in pediatric patients by the inulin single-bolus-injection method. Methods: Complete inulin plasma concentration-time curves of 154 patients were divided into an index (n = 100) and a validation set (n = 54). A population pharmacokinetic model was developed for the index set. Optimal sampling times were selected based on D-optimality theory. For the validation set, Bayesian estimates of clearance were generated using the derived population parameters and concentrations at two to four sampling times. Bayesian estimates of clearance were compared with the individual reference values of clearance. Results: The strategies with samples taken at 10/30/90/240 min, 10/30/240 min, 10/90/240 min, 30/90/240 min, and 90/240 min allowed accurate prediction of inulin clearance (bias <3% and not significantly different from 0; imprecision <15%). Conclusions: Strategies involving two to four samples, including a sample at 240 min after administration of inulin, in the inulin single-injection method allow accurate prediction of inulin clearance in pediatric patients. Even one blood sample at 240 min showed acceptable performance. The proposed strategies are practical and convenient to children, and reduce repetitive blood sampling without compromising accuracy.

scholarly journals Optimal sampling strategies for darunavir and external validation of the underlying population pharmacokinetic model

2020 ◽  
Author(s):  
Gabriel Stillemans ◽  
Leila Belkhir ◽  
Bernard Vandercam ◽  
Anne Vincent ◽  
Vincent Haufroid ◽  
...  
Keyword(s):  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
External Validation ◽  
Diagnostic Methods ◽  
Validation Dataset ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Optimal Sampling ◽  
Sampling Strategies ◽  
Validation Set

Abstract Purpose A variety of diagnostic methods are available to validate the performance of population pharmacokinetic models. Internal validation, which applies these methods to the model building dataset and to additional data generated through Monte Carlo simulations, is often sufficient, but external validation, which requires a new dataset, is considered a more rigorous approach, especially if the model is to be used for predictive purposes. Our first objective was to validate a previously published population pharmacokinetic model of darunavir, an HIV protease inhibitor boosted with ritonavir or cobicistat. Our second objective was to use this model to derive optimal sampling strategies that maximize the amount of information collected with as few pharmacokinetic samples as possible. Methods A validation dataset comprising 164 sparsely sampled individuals using ritonavir-boosted darunavir was used for validation. Standard plots of predictions and residuals, NPDE, visual predictive check, and bootstrapping were applied to both the validation set and the combined learning/validation set in NONMEM to assess model performance. D-optimal designs for darunavir were then calculated in PopED and further evaluated in NONMEM through simulations. Results External validation confirmed model robustness and accuracy in most scenarios but also highlighted several limitations. The best one-, two-, and three-point sampling strategies were determined to be pre-dose (0 h); 0 and 4 h; and 1, 4, and 19 h, respectively. A combination of samples at 0, 1, and 4 h was comparable to the optimal three-point strategy. These could be used to reliably estimate individual pharmacokinetic parameters, although with fewer samples, precision decreased and the number of outliers increased significantly. Conclusions Optimal sampling strategies derived from this model could be used in clinical practice to enhance therapeutic drug monitoring or to conduct additional pharmacokinetic studies.

scholarly journals Development and evaluation of a Bayesian pharmacokinetic estimator and optimal, sparse sampling strategies for ceftazidime.

1996 ◽  
Vol 40 (8) ◽  
pp. 1860-1865 ◽  
Author(s):  
A D Kashuba ◽  
C H Ballow ◽  
A Forrest
Keyword(s):  
Sampling Strategy ◽  
Population Pharmacokinetic Analysis ◽  
Volume Of Distribution ◽  
Sparse Sampling ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Optimal Sampling ◽  
Sampling Strategies ◽  
Adaptive Feedback ◽  
Sampling Times

Data were gathered during an activity-controlled trial in which seriously ill, elderly patients were randomized to receive intravenous ceftazidime or ciprofloxacin and for which adaptive feedback control of drug concentrations in plasma and activity profiles was prospectively performed. The adaptive feedback control algorithm for ceftazidime used an initial population model, a maximum a posteriori (MAP)-Bayesian pharmacokinetic parameter value estimator, and an optimal, sparse sampling strategy for ceftazidime that had been derived from data in the literature obtained from volunteers. Iterative two-stage population pharmacokinetic analysis was performed to develop an unbiased MAP-Bayesian estimator and updated optimal, sparse sampling strategies. The final median values of the population parameters were follows: the volume of distribution of the central compartment was equal to 0.249 liter/kg, the volume of distribution of the peripheral compartment was equal to 0.173 liter/kg, the distributional clearance between the central and peripheral compartments was equal to 0.2251 liter/h/kg, the slope of the total clearance (CL) versus the creatinine clearance (CLCR) was equal to 0.000736 liter/h/kg of CL/1 ml/min/1.73 m2 of CLCR, and nonrenal clearance was equal to + 0.00527 liter/h/kg. Optimal sampling times were dependent on CLCR; for CLCR of > or = 30 ml/min/1.73 m2, the optimal sampling times were 0.583, 3.0, 7.0, and 16.0 h and, for CLCR of < 30 ml/min/1.73 m2, optimal sampling times were 0.583, 4.15, 11.5, and 24.0 h. The study demonstrates that because pharmacokinetic information from volunteers may often not be reflective of specialty populations such as critically ill elderly individuals, iterative two-stage population pharmacokinetic analysis, MAP-Bayesian parameter estimation, and optimal, sparse sampling strategy can be important tools in characterizing their pharmacokinetics.

Practical Approach for Determining Glomerular Filtration Rate by Single-Injection Inulin Clearance

1992 ◽  
Vol 38 (3) ◽  
pp. 403-407 ◽  
Author(s):  
K Jung ◽  
W Henke ◽  
B D Schulze ◽  
K Sydow ◽  
K Precht ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Bolus Injection ◽  
Single Injection ◽  
Compartment Model ◽  
Inulin Clearance ◽  
Analytical Sensitivity ◽  
Blood Samples ◽  
Isotope Technique

Abstract We compared the glomerular filtration rate as measured by a single-injection inulin clearance with that measured by a standard isotope method with 99mTc-labeled diethylenetriaminopentaacetic acid in 21 subjects with glomerular filtration rates greater than 35 mL/min. After a bolus injection of 5 g of inulin, blood samples were taken 20, 45, 90, 120, 145, 180, and 240 min afterwards. Inulin was measured by optimized chemical or enzymatic methods of high analytical sensitivity to determine inulin at low concentrations. We used the one-compartment model and inulin concentrations measured at two sampling times to calculate the glomerular filtration rate from the data of the disappearance curve of inulin. Inulin concentrations at 20 and 240 min after injection of the inulin bolus were suited to estimate glomerular filtration rate by this procedure, resulting in values (y) comparable with those obtained by isotope technique (x). The relationship to the isotope technique was characterized by the equation y = +4.80 mL/min + 0.92x (r = 0.97). The single-injection inulin clearance determination can detect a decrease of glomerular filtration rate at the beginning of kidney damage, given that our study included subjects with glomerular filtration rates greater than 35 mL/min. We conclude that the glomerular filtration rate can be determined by analyzing only two blood samples after a bolus injection of inulin.

The Anticoagulant Effect of Heparinoid Org 10172 During Haemodialysis: An Objective Assessment

1986 ◽  
Vol 55 (02) ◽  
pp. 271-275 ◽  
Author(s):  
Helen Ireland ◽  
D A Lane ◽  
Angela Flynn ◽  
E Anastassiades ◽  
J R Curtis
Keyword(s):  
Renal Failure ◽  
Bolus Dose ◽  
Bolus Injection ◽  
Objective Assessment ◽  
Factor Xa ◽  
Fibrin Clot ◽  
Natural Origin ◽  
Fibrin Formation ◽  
Single Bolus Injection

SummaryThe heparinoid of natural origin Org 10172 has anti-factor Xa activity but minimal anti-thrombin activity, and little effect upon broad spectrum assays such as the KCCT in vitro. Its anticoagulant effects have been compared to those of commercial heparin in 7 patients undergoing haemodialysis for chronic renal failure. Commercial heparin was administered in a dose (5,000 iu bolus + 1,500 iu/hour continuous iv infusion) previously shown to inhibit fibrin formation during haemodialysis. This produced mean anti-factor Xa levels in plasma between 0.7-1.0 iu/ml and largely suppressed fibrin formation for 5 h dialysis measured as mean FPA levels in plasma. Administration of Org 10172 as a bolus of 1,350 anti-factor Xa u or 2,000-2,400 anti-factor Xa u produced plasma anti-factor Xa levels of less than 0.5 u/ml and allowed fibrin clot and FPA generation during dialysis. Org 10172 administered as a bolus dose of 4,000-4,800 anti-factor Xa u produced mean anti-factor Xa levels of greater than 0.5 u/ml, allowed dialysis of 6 patients for 5 h and appreciably suppressed FPA generation during dialysis, with little effect on the KCCT.It is concluded that the anti-factor Xa activity of Org 10172 may reflect its ability to inhibit fibrin during dialysis and that single bolus injection of Org 10172 may be a useful alternative method of achieving anticoagulation.

scholarly journals Optimal Sampling Strategies for Detecting Zoonotic Disease Epidemics

2014 ◽  
Vol 10 (6) ◽  
pp. e1003668 ◽  
Author(s):  
Jake M. Ferguson ◽  
Jessica B. Langebrake ◽  
Vincent L. Cannataro ◽  
Andres J. Garcia ◽  
Elizabeth A. Hamman ◽  
...  
Keyword(s):  
Zoonotic Disease ◽  
Optimal Sampling ◽  
Sampling Strategies ◽  
Disease Epidemics

Iloprost improves femoro-distal graft flow after a single bolus injection

1991 ◽  
Vol 5 (1) ◽  
pp. 19-22 ◽  
Author(s):  
N.C. Hickey ◽  
C.P. Shearman ◽  
M.C. Crowson ◽  
M.H. Simms ◽  
H.R. Watson
Keyword(s):  
Bolus Injection ◽  
Single Bolus ◽  
Graft Flow ◽  
Single Bolus Injection

scholarly journals Pharmacokinetic Modeling and Optimal Sampling Strategies for Therapeutic Drug Monitoring of Rifampin in Patients with Tuberculosis

2015 ◽  
Vol 59 (8) ◽  
pp. 4907-4913 ◽  
Author(s):  
Marieke G. G. Sturkenboom ◽  
Leonie W. Mulder ◽  
Arthur de Jager ◽  
Richard van Altena ◽  
Rob E. Aarnoutse ◽  
...  
Keyword(s):  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Mean Squared Error ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Optimal Sampling ◽  
Sampling Strategies ◽  
Wide Range

ABSTRACTRifampin, together with isoniazid, has been the backbone of the current first-line treatment of tuberculosis (TB). The ratio of the area under the concentration-time curve from 0 to 24 h (AUC0–24) to the MIC is the best predictive pharmacokinetic-pharmacodynamic parameter for determinations of efficacy. The objective of this study was to develop an optimal sampling procedure based on population pharmacokinetics to predict AUC0–24values. Patients received rifampin orally once daily as part of their anti-TB treatment. A one-compartmental pharmacokinetic population model with first-order absorption and lag time was developed using observed rifampin plasma concentrations from 55 patients. The population pharmacokinetic model was developed using an iterative two-stage Bayesian procedure and was cross-validated. Optimal sampling strategies were calculated using Monte Carlo simulation (n= 1,000). The geometric mean AUC0–24value was 41.5 (range, 13.5 to 117) mg · h/liter. The median time to maximum concentration of drug in serum (Tmax) was 2.2 h, ranging from 0.4 to 5.7 h. This wide range indicates that obtaining a concentration level at 2 h (C2) would not capture the peak concentration in a large proportion of the population. Optimal sampling using concentrations at 1, 3, and 8 h postdosing was considered clinically suitable with anr2value of 0.96, a root mean squared error value of 13.2%, and a prediction bias value of −0.4%. This study showed that the rifampin AUC0–24in TB patients can be predicted with acceptable accuracy and precision using the developed population pharmacokinetic model with optimal sampling at time points 1, 3, and 8 h.

scholarly journals Correlation of plasma concentrations of cystatin C and creatinine to inulin clearance in a pediatric population

1998 ◽  
Vol 44 (6) ◽  
pp. 1334-1338 ◽  
Author(s):  
Douglas Stickle ◽  
Barbara Cole ◽  
Karl Hock ◽  
Keith A Hruska ◽  
Mitchell G Scott
Keyword(s):  
Correlation Coefficient ◽  
Cystatin C ◽  
Linear Correlation ◽  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Age Groups ◽  
Inulin Clearance ◽  
Blood Concentrations ◽  
Group A ◽  
Group B

Abstract Measurement of blood concentrations of cystatin C (cysC), a cysteine protease inhibitor present in human plasma, has been suggested for use as an indicator of glomerular filtration rate (GFR) in a manner analogous to the use of plasma creatinine (SCR). In this study, cysC and SCR were measured in plasma from pediatric patients (4–19 years) with renal disease for whom a “gold standard” measurement of GFR via inulin clearance (CIN) was available. The data analyses were divided into two age groups: group A (4–12 years, n = 26) and group B (12–19 years, n = 34). For both age groups, the linear correlation coefficient of [cysC]−1 vs CIN (mL/min/1.73 m2) (r = 0.765 for group A and r = 0.869 for group B) was less than that of the linear correlation coefficient of [SCR]−1 vs CIN (r = 0.841 for group A and r = 0.892 for group B). As a single measurement for detection of abnormal GFR, however, the optimum receiver-operator characteristic point for cysC measurement (for group A at cysC &gt;1.2 mg/L, sensitivity = 80%, specificity = 91%; and for group B at cysC &gt;1.4 mg/L, sensitivity = 87%, specificity = 100%) was numerically superior to that for SCR measurement (for group A at SCR &gt;8.0 mg/L, sensitivity = 67%, specificity = 100%; and for group B at SCR &gt;9.0 mg/L, sensitivity = 91%, specificity = 91%), using a reference value for normal GFR of CIN &gt; 90 mL/min/1.73 m2. However, these differences were not statistically significant. CysC measurement appears to be broadly equivalent to SCR measurement for estimation of GFR in pediatric patients.

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