Correlations between cortisol level and internalizing disposition of young children are increased by selecting optimal sampling times and aggregating data

2007 ◽  
Vol 49 (6) ◽  
pp. 633-639 ◽  
Author(s):  
Ishien Li ◽  
Hua-Huei Chiou ◽  
Pao-Sheng Shen
2019 ◽  
Vol 22 ◽  
pp. 112-121 ◽  
Author(s):  
Esther Oyaga-Iriarte ◽  
Asier Insausti ◽  
Lorea Bueno ◽  
Onintza Sayar ◽  
Azucena Aldaz

Purpose: The present study was performed to demonstrate that small amounts of routine clinical data allow to generate valuable knowledge. Concretely, the aims of this research were to build a joint population pharmacokinetic model for capecitabine and three of its metabolites (5-DFUR, 5-FU and 5-FUH2) and to determine optimal sampling times for therapeutic drug monitoring. Methods: We used data of 7 treatment cycles of capecitabine in patients with metastatic colorectal cancer. The population pharmacokinetic model was built as a multicompartmental model using NONMEM and was internally validated by visual predictive check. Optimal sampling times were estimated using PFIM 4.0 following D-optimality criterion. Results: The final model was a multicompartmental model which represented the sequential transformations from capecitabine to its metabolites 5-DFUR, 5-FU and 5-FUH2 and was correctly validated. The optimal sampling times were 0.546, 0.892, 1.562, 4.736 and 8 hours after the administration of the drug. For its correct implementation in clinical practice, the values were rounded to 0.5, 1, 1.5, 5 and 8 hours after the administration of the drug. Conclusions: Capecitabine, 5-DFUR, 5-FU and 5-FUH2 can be correctly described by the joint multicompartmental model presented in this work. The aforementioned times are optimal to maximize the information of samples. Useful knowledge can be obtained for clinical practice from small databases.


2003 ◽  
Vol 49 (7) ◽  
pp. 1170-1179 ◽  
Author(s):  
Lyonne K van Rossum ◽  
Ron A A Mathot ◽  
Karlien Cransberg ◽  
Arnold G Vulto

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.


2012 ◽  
Vol 52 (1) ◽  
pp. 43-57 ◽  
Author(s):  
Cyrielle Dumont ◽  
France Mentré ◽  
Clare Gaynor ◽  
Karl Brendel ◽  
Charlotte Gesson ◽  
...  

1997 ◽  
Vol 31 (9) ◽  
pp. 980-983 ◽  
Author(s):  
Aaron H Burstein ◽  
Peter Gal ◽  
Alan Forrest

Objective To use optimal sampling theory to determine the fewest vancomycin concentrations required and the appropriate sampling times to calculate vancomycin pharmacokinetic parameters in neonates. Design Unblinded evaluation in neonates with presumed sepsis. Setting Level 3 community-based neonatal intensive care unit. Patients Eleven neonates with presumed sepsis. Interventions Twelve courses of intravenous vancomycin 20 mg/kg were administered. Blood samples were collected 3 and 9 hours after initiation of a 1-hour infusion of the first dose. Measurements and Main Results A two-compartment model was fit to vancomycin concentrations using iterative two-stage analysis. Pharmacokinetic parameter estimates were used for determination of optimal sampling times for two-, three-, and four-sample strategies with subsequent generation of two-, three-, and four-sample concentration data for 100 cases. Relative performance of strategies was compared through calculation and comparison of D efficiency for the determined strategies. Bias (median percent error) and precision (median percent absolute error) of pharmacokinetic parameter estimates for each strategy in the 100 simulated cases were determined. Conclusions For estimation of total clearance and volume in the central and peripheral compartments, all strategies performed similarly with no difference in efficiency or bias and precision of estimates. Our results suggest that for clinical evaluations two appropriately timed samples (0.5 h after a 1-h infusion, trough concentration) are adequate for estimation of vancomycin clearance in neonates.


1995 ◽  
Vol 34 (04) ◽  
pp. 156-160
Author(s):  
D. Lüscher ◽  
S. Lourens ◽  
H. Rösier ◽  
P. Koranda

SummaryOrthoiodohippurate (OIH) clearance data obtained with the two-compartment/two-sample method of Lear which uses varying sampling time combinations, were compared with those of the reference two-compartment/multi-sample method of Sapirstein. A total of 35 studies were performed in 33 adult patients. The OIH clearance values determined by the reference method ranged from 107 to 883 ml/min/1.73 m2, with a median of 406 ml/min/1.73 m2. It was ascertained that the precision of the Lear method is partially dependent upon the sampling time combination. The most reliable results with the Lear method in this patient population were obtained by taking a first sample at approximately 8 min p. L, and a second sample at 32 min p. i. or later.


2020 ◽  
Vol 75 (11) ◽  
pp. 3293-3302 ◽  
Author(s):  
Rashmi V Shingde ◽  
Stephanie E Reuter ◽  
Garry G Graham ◽  
Jane E Carland ◽  
Kenneth M Williams ◽  
...  

Abstract Background Current guidelines for intravenous vancomycin identify drug exposure (as indicated by the AUC) as the best pharmacokinetic (PK) indicator of therapeutic outcome. Objectives To assess the accuracy of two Bayesian forecasting programs in estimating vancomycin AUC0–∞ in adults with limited blood concentration sampling. Methods The application of seven vancomycin population PK models in two Bayesian forecasting programs was examined in non-obese adults (n = 22) with stable renal function. Patients were intensively sampled following a single (1000 mg or 15 mg/kg) dose. For each patient, AUC was calculated by fitting all vancomycin concentrations to a two-compartment model (defined as AUCTRUE). AUCTRUE was then compared with the Bayesian-estimated AUC0–∞ values using a single vancomycin concentration sampled at various times post-infusion. Results Optimal sampling times varied across different models. AUCTRUE was generally overestimated at earlier sampling times and underestimated at sampling times after 4 h post-infusion. The models by Goti et al. (Ther Drug Monit 2018; 40 212–21) and Thomson et al. (J Antimicrob Chemother 2009; 63 1050–7) had precise and unbiased sampling times (defined as mean imprecision <25% and <38 mg·h/L, with 95% CI for mean bias containing zero) between 1.5 and 6 h and between 0.75 and 2 h post-infusion, respectively. Precise but biased sampling times for Thomson et al. were between 4 and 6 h post-infusion. Conclusions When using a single vancomycin concentration for Bayesian estimation of vancomycin drug exposure (AUC), the predictive performance was generally most accurate with sample collection between 1.5 and 6 h after infusion, though optimal sampling times varied across different population PK models.


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