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05-05-2024 | Tobramycin | Original Research Article

Does Sample Size, Sampling Strategy, or Handling of Concentrations Below the Lower Limit of Quantification Matter When Externally Evaluating Population Pharmacokinetic Models?

Authors: Mehdi El Hassani, Uwe Liebchen, Amélie Marsot

Published in: European Journal of Drug Metabolism and Pharmacokinetics | Issue 4/2024

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Abstract

Background and Objectives

Precision dosing requires selecting the appropriate population pharmacokinetic model, which can be assessed through external evaluations (EEs). The lack of understanding of how different study design factors influence EE study outcomes makes it challenging to select the most suitable model for clinical use. This study aimed to evaluate the impact of sample size, sampling strategy, and handling of concentrations below the lower limit of quantification (BLQ) on the outcomes of EE for four population pharmacokinetic models using vancomycin and tobramycin as examples.

Methods

Three virtual patient populations undergoing vancomycin or tobramycin therapy were simulated with varying sample size and sampling scenarios. The three approaches used to handle BLQ data were to (1) discard them, (2) impute them as LLOQ/2, or (3) use a likelihood-based approach. EEs were performed with NONMEM and R.

Results

Sample size did not have an important impact on the EE results for a given scenario. Increasing the number of samples per patient did not improve predictive performance for two out of the three evaluated models. Evaluating a model developed with rich sampling did not result in better performance than those developed with regular therapeutic drug monitoring. A likelihood-based method to handle BLQ samples impacted the outcomes of the EE with lower bias for predicted troughs.

Conclusions

This study suggests that a large sample size may not be necessary for an EE study, and models selected based on TDM may be more generalizable. The study highlights the need for guidelines for EE of population pharmacokinetic models for clinical use.
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Literature
1.
go back to reference Marsot A. Pharmacokinetic variability in pediatrics and intensive care: toward a personalized dosing approach. J Pharm Pharm Sci. 2018;21(1):354–62.PubMedCrossRef Marsot A. Pharmacokinetic variability in pediatrics and intensive care: toward a personalized dosing approach. J Pharm Pharm Sci. 2018;21(1):354–62.PubMedCrossRef
2.
go back to reference Powell JR, Cook J, Wang Y, Peck R, Weiner D. Drug dosing recommendations for all patients: a roadmap for change. Clin Pharmacol Ther. 2021;109(1):65–72.PubMedCrossRef Powell JR, Cook J, Wang Y, Peck R, Weiner D. Drug dosing recommendations for all patients: a roadmap for change. Clin Pharmacol Ther. 2021;109(1):65–72.PubMedCrossRef
3.
go back to reference Mould DR, Upton RN. Basic concepts in population modeling, simulation, and model-based drug development-part 2: introduction to pharmacokinetic modeling methods. CPT Pharmacomet Syst Pharmacol. 2013;2(4): e38.CrossRef Mould DR, Upton RN. Basic concepts in population modeling, simulation, and model-based drug development-part 2: introduction to pharmacokinetic modeling methods. CPT Pharmacomet Syst Pharmacol. 2013;2(4): e38.CrossRef
4.
go back to reference Kantasiripitak W, Van Daele R, Gijsen M, Ferrante M, Spriet I, Dreesen E. Software tools for model-informed precision dosing: how well do they satisfy the needs? Front Pharmacol. 2020;11:620.PubMedPubMedCentralCrossRef Kantasiripitak W, Van Daele R, Gijsen M, Ferrante M, Spriet I, Dreesen E. Software tools for model-informed precision dosing: how well do they satisfy the needs? Front Pharmacol. 2020;11:620.PubMedPubMedCentralCrossRef
5.
go back to reference Aljutayli A, Thirion DJG, Bonnefois G, Nekka F. Pharmacokinetic equations versus Bayesian guided vancomycin monitoring: pharmacokinetic model and model-informed precision dosing trial simulations. Clin Transl Sci. 2022;15(4):942–53.PubMedPubMedCentralCrossRef Aljutayli A, Thirion DJG, Bonnefois G, Nekka F. Pharmacokinetic equations versus Bayesian guided vancomycin monitoring: pharmacokinetic model and model-informed precision dosing trial simulations. Clin Transl Sci. 2022;15(4):942–53.PubMedPubMedCentralCrossRef
6.
go back to reference Gu JQ, Guo YP, Jiao Z, Ding JJ, Li GF. How to handle delayed or missed doses: a population pharmacokinetic perspective. Eur J Drug Metab Pharmacokinet. 2020;45(2):163–72.PubMedCrossRef Gu JQ, Guo YP, Jiao Z, Ding JJ, Li GF. How to handle delayed or missed doses: a population pharmacokinetic perspective. Eur J Drug Metab Pharmacokinet. 2020;45(2):163–72.PubMedCrossRef
7.
go back to reference Patanwala AE, Spremo D, Jeon M, Thoma Y, Alffenaa JWC, Stocker S. Discrepancies between Bayesian vancomycin models can affect clinical decisions in the critically ill. Crit Care Res Pract. 2022;2022:7011376.PubMedPubMedCentral Patanwala AE, Spremo D, Jeon M, Thoma Y, Alffenaa JWC, Stocker S. Discrepancies between Bayesian vancomycin models can affect clinical decisions in the critically ill. Crit Care Res Pract. 2022;2022:7011376.PubMedPubMedCentral
8.
go back to reference El Hassani M, Marsot A. External evaluation of population pharmacokinetic models for precision dosing: current state and knowledge gaps. Clin Pharmacokinet. 2023;62(4):533–40.PubMedCrossRef El Hassani M, Marsot A. External evaluation of population pharmacokinetic models for precision dosing: current state and knowledge gaps. Clin Pharmacokinet. 2023;62(4):533–40.PubMedCrossRef
9.
go back to reference Cheng Y, Wang C-Y, Li Z-R, Pan Y, Liu M-B, Jiao Z. Can population pharmacokinetics of antibiotics be extrapolated? Implications of external evaluations. Clin Pharmacokinet. 2021;60(1):53–68.PubMedCrossRef Cheng Y, Wang C-Y, Li Z-R, Pan Y, Liu M-B, Jiao Z. Can population pharmacokinetics of antibiotics be extrapolated? Implications of external evaluations. Clin Pharmacokinet. 2021;60(1):53–68.PubMedCrossRef
10.
go back to reference Kim YK, Lee JH, Jang HJ, Zang DY, Lee DH. Predicting antibiotic effect of vancomycin using pharmacokinetic/pharmacodynamic modeling and simulation: dense sampling versus sparse sampling. Antibiotics (Basel). 2022;11(6):743.PubMedCrossRef Kim YK, Lee JH, Jang HJ, Zang DY, Lee DH. Predicting antibiotic effect of vancomycin using pharmacokinetic/pharmacodynamic modeling and simulation: dense sampling versus sparse sampling. Antibiotics (Basel). 2022;11(6):743.PubMedCrossRef
11.
go back to reference Aarons L, Ogungbenro K. Optimal design of pharmacokinetic studies. Basic Clin Pharmacol Toxicol. 2010;106(3):250–5.PubMedCrossRef Aarons L, Ogungbenro K. Optimal design of pharmacokinetic studies. Basic Clin Pharmacol Toxicol. 2010;106(3):250–5.PubMedCrossRef
12.
go back to reference Beal SL. Sample size determination for confidence intervals on the population mean and on the difference between two population means. Biometrics. 1989;45(3):969–77.PubMedCrossRef Beal SL. Sample size determination for confidence intervals on the population mean and on the difference between two population means. Biometrics. 1989;45(3):969–77.PubMedCrossRef
14.
go back to reference Ogungbenro K, Aarons L. How many subjects are necessary for population pharmacokinetic experiments? Confidence interval approach. Eur J Clin Pharmacol. 2008;64(7):705–13.PubMedCrossRef Ogungbenro K, Aarons L. How many subjects are necessary for population pharmacokinetic experiments? Confidence interval approach. Eur J Clin Pharmacol. 2008;64(7):705–13.PubMedCrossRef
15.
go back to reference Chan Kwong AHXP, Calvier EAM, Fabre D, Gattacceca F, Khier S. Prior information for population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine. J Pharmacokinet Pharmacodyn. 2020;47(5):431–46.PubMedPubMedCentralCrossRef Chan Kwong AHXP, Calvier EAM, Fabre D, Gattacceca F, Khier S. Prior information for population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine. J Pharmacokinet Pharmacodyn. 2020;47(5):431–46.PubMedPubMedCentralCrossRef
16.
go back to reference Keizer RJ, Jansen RS, Rosing H, Thijssen B, Beijnen JH, Schellens JH, et al. Incorporation of concentration data below the limit of quantification in population pharmacokinetic analyses. Pharmacol Res Perspect. 2015;3(2): e00131.PubMedPubMedCentralCrossRef Keizer RJ, Jansen RS, Rosing H, Thijssen B, Beijnen JH, Schellens JH, et al. Incorporation of concentration data below the limit of quantification in population pharmacokinetic analyses. Pharmacol Res Perspect. 2015;3(2): e00131.PubMedPubMedCentralCrossRef
17.
go back to reference Huang S, Ding Q, Yang N, Sun Z, Cheng Q, Liu W, et al. External evaluation of published population pharmacokinetic models of posaconazole. Front Pharmacol. 2022;13:1005348.PubMedPubMedCentralCrossRef Huang S, Ding Q, Yang N, Sun Z, Cheng Q, Liu W, et al. External evaluation of published population pharmacokinetic models of posaconazole. Front Pharmacol. 2022;13:1005348.PubMedPubMedCentralCrossRef
18.
go back to reference Konecki C, Feliu C, Cazaubon Y, Giusti D, Tonye-Libyh M, Brixi H, et al. External evaluation of population pharmacokinetic models and bayes-based dosing of infliximab. Pharmaceutics. 2021;13(8):1191.PubMedPubMedCentralCrossRef Konecki C, Feliu C, Cazaubon Y, Giusti D, Tonye-Libyh M, Brixi H, et al. External evaluation of population pharmacokinetic models and bayes-based dosing of infliximab. Pharmaceutics. 2021;13(8):1191.PubMedPubMedCentralCrossRef
19.
go back to reference Beal SL. Ways to fit a PK model with some data below the quantification limit. J Pharmacokinet Pharmacodyn. 2001;28(5):481–504.PubMedCrossRef Beal SL. Ways to fit a PK model with some data below the quantification limit. J Pharmacokinet Pharmacodyn. 2001;28(5):481–504.PubMedCrossRef
20.
go back to reference Santacana E, Rodríguez-Alonso L, Padullés A, Guardiola J, Rodríguez-Moranta F, Serra K, et al. External evaluation of population pharmacokinetic models of infliximab in patients with inflammatory bowel disease. Ther Drug Monit. 2018;40(1):120–9.PubMedCrossRef Santacana E, Rodríguez-Alonso L, Padullés A, Guardiola J, Rodríguez-Moranta F, Serra K, et al. External evaluation of population pharmacokinetic models of infliximab in patients with inflammatory bowel disease. Ther Drug Monit. 2018;40(1):120–9.PubMedCrossRef
21.
go back to reference Hanafin PO, Nation RL, Scheetz MH, Zavascki AP, Sandri AM, Kwa AL, et al. Assessing the predictive performance of population pharmacokinetic models for intravenous polymyxin B in critically ill patients. CPT Pharmacomet Syst Pharmacol. 2021;10(12):1525–37.CrossRef Hanafin PO, Nation RL, Scheetz MH, Zavascki AP, Sandri AM, Kwa AL, et al. Assessing the predictive performance of population pharmacokinetic models for intravenous polymyxin B in critically ill patients. CPT Pharmacomet Syst Pharmacol. 2021;10(12):1525–37.CrossRef
22.
go back to reference Yang N, Wang J, Xie Y, Ding J, Wu C, Liu J, et al. External evaluation of population pharmacokinetic models to inform precision dosing of meropenem in critically ill patients. Front Pharmacol. 2022;13: 838205.PubMedPubMedCentralCrossRef Yang N, Wang J, Xie Y, Ding J, Wu C, Liu J, et al. External evaluation of population pharmacokinetic models to inform precision dosing of meropenem in critically ill patients. Front Pharmacol. 2022;13: 838205.PubMedPubMedCentralCrossRef
23.
go back to reference Nguyen TH, Comets E, Mentré F. Extension of NPDE for evaluation of nonlinear mixed effect models in presence of data below the quantification limit with applications to HIV dynamic model. J Pharmacokinet Pharmacodyn. 2012;39(5):499–518.PubMedCrossRef Nguyen TH, Comets E, Mentré F. Extension of NPDE for evaluation of nonlinear mixed effect models in presence of data below the quantification limit with applications to HIV dynamic model. J Pharmacokinet Pharmacodyn. 2012;39(5):499–518.PubMedCrossRef
24.
go back to reference Irby DJ, Ibrahim ME, Dauki AM, Badawi MA, Illamola SM, Chen M, et al. Approaches to handling missing or “problematic” pharmacology data: pharmacokinetics. CPT Pharmacomet Syst Pharmacol. 2021;10(4):291–308.CrossRef Irby DJ, Ibrahim ME, Dauki AM, Badawi MA, Illamola SM, Chen M, et al. Approaches to handling missing or “problematic” pharmacology data: pharmacokinetics. CPT Pharmacomet Syst Pharmacol. 2021;10(4):291–308.CrossRef
25.
go back to reference Ahn JE, Karlsson MO, Dunne A, Ludden TM. Likelihood based approaches to handling data below the quantification limit using NONMEM VI. J Pharmacokinet Pharmacodyn. 2008;35(4):401–21.PubMedCrossRef Ahn JE, Karlsson MO, Dunne A, Ludden TM. Likelihood based approaches to handling data below the quantification limit using NONMEM VI. J Pharmacokinet Pharmacodyn. 2008;35(4):401–21.PubMedCrossRef
27.
go back to reference Mehrotra N, Tang L, Phelps SJ, Meibohm B. Evaluation of vancomycin dosing regimens in preterm and term neonates using Monte Carlo simulations. Pharmacotherapy. 2012;32(5):408–19.PubMedCrossRef Mehrotra N, Tang L, Phelps SJ, Meibohm B. Evaluation of vancomycin dosing regimens in preterm and term neonates using Monte Carlo simulations. Pharmacotherapy. 2012;32(5):408–19.PubMedCrossRef
28.
go back to reference Dong M, Rodriguez AV, Blankenship CA, McPhail G, Vinks AA, Hunter LL. Pharmacokinetic modelling to predict risk of ototoxicity with intravenous tobramycin treatment in cystic fibrosis. J Antimicrob Chemother. 2021;76(11):2923–31.PubMedPubMedCentralCrossRef Dong M, Rodriguez AV, Blankenship CA, McPhail G, Vinks AA, Hunter LL. Pharmacokinetic modelling to predict risk of ototoxicity with intravenous tobramycin treatment in cystic fibrosis. J Antimicrob Chemother. 2021;76(11):2923–31.PubMedPubMedCentralCrossRef
29.
go back to reference El Hassani M, Simard C, Pilote S, Cloutier I, Soufsaf S, Marsot A. Consideration of height-based tobramycin dosing regimens for the treatment of adult cystic fibrosis pulmonary exacerbations. Br J Clin Pharmacol. 2021;88(5):2246–55.PubMedCrossRef El Hassani M, Simard C, Pilote S, Cloutier I, Soufsaf S, Marsot A. Consideration of height-based tobramycin dosing regimens for the treatment of adult cystic fibrosis pulmonary exacerbations. Br J Clin Pharmacol. 2021;88(5):2246–55.PubMedCrossRef
30.
go back to reference Smit C, Wasmann RE, Wiezer MJ, van Dongen HPA, Mouton JW, Brüggemann RJM, et al. Tobramycin clearance is best described by renal function estimates in obese and non-obese individuals: results of a prospective rich sampling pharmacokinetic study. Pharm Res. 2019;36(8):112.PubMedPubMedCentralCrossRef Smit C, Wasmann RE, Wiezer MJ, van Dongen HPA, Mouton JW, Brüggemann RJM, et al. Tobramycin clearance is best described by renal function estimates in obese and non-obese individuals: results of a prospective rich sampling pharmacokinetic study. Pharm Res. 2019;36(8):112.PubMedPubMedCentralCrossRef
32.
go back to reference Alghanem S, Paterson I, Touw DJ, Thomson AH. Influence of multiple courses of therapy on aminoglycoside clearance in adult patients with cystic fibrosis. J Antimicrob Chemother. 2013;68(6):1338–47.PubMedCrossRef Alghanem S, Paterson I, Touw DJ, Thomson AH. Influence of multiple courses of therapy on aminoglycoside clearance in adult patients with cystic fibrosis. J Antimicrob Chemother. 2013;68(6):1338–47.PubMedCrossRef
33.
go back to reference Teutonico D, Musuamba F, Maas HJ, Facius A, Yang S, Danhof M, et al. Generating virtual patients by multivariate and discrete re-sampling techniques. Pharm Res. 2015;32(10):3228–37.PubMedPubMedCentralCrossRef Teutonico D, Musuamba F, Maas HJ, Facius A, Yang S, Danhof M, et al. Generating virtual patients by multivariate and discrete re-sampling techniques. Pharm Res. 2015;32(10):3228–37.PubMedPubMedCentralCrossRef
34.
go back to reference Owen JS, Fiedler-Kelly J (2014) Introduction to population pharmacokinetic/pharmacodynamic analysis with nonlinear mixed effects models. John Wiley & Sons, Hoboken, NJ Owen JS, Fiedler-Kelly J (2014) Introduction to population pharmacokinetic/pharmacodynamic analysis with nonlinear mixed effects models. John Wiley & Sons, Hoboken, NJ
35.
go back to reference Germovsek E, Osborne L, Gunaratnam F, Lounis SA, Busquets FB, Standing JF, et al. Development and external evaluation of a population pharmacokinetic model for continuous and intermittent administration of vancomycin in neonates and infants using prospectively collected data. J Antimicrob Chemother. 2019;74(4):1003–11.PubMedCrossRef Germovsek E, Osborne L, Gunaratnam F, Lounis SA, Busquets FB, Standing JF, et al. Development and external evaluation of a population pharmacokinetic model for continuous and intermittent administration of vancomycin in neonates and infants using prospectively collected data. J Antimicrob Chemother. 2019;74(4):1003–11.PubMedCrossRef
36.
go back to reference Vancocin (vancomycin hydrochloride) [package insert]. Baudette, MN: ANI Pharmaceuticals; 2017 Vancocin (vancomycin hydrochloride) [package insert]. Baudette, MN: ANI Pharmaceuticals; 2017
37.
go back to reference Aljutayli A, El-Haffaf I, Marsot A, Nekka F. An update on population pharmacokinetic analyses of vancomycin, part II: in pediatric patients. Clin Pharmacokinet. 2022;61(1):47–70.PubMedCrossRef Aljutayli A, El-Haffaf I, Marsot A, Nekka F. An update on population pharmacokinetic analyses of vancomycin, part II: in pediatric patients. Clin Pharmacokinet. 2022;61(1):47–70.PubMedCrossRef
38.
go back to reference Smit C, Wasmann RE, Goulooze SC, Hazebroek EJ, Van Dongen EPA, Burgers DMT, et al. A prospective clinical study characterizing the influence of morbid obesity on the pharmacokinetics of gentamicin: towards individualized dosing in obese patients. Clin Pharmacokinet. 2019;58(10):1333–43.PubMedPubMedCentralCrossRef Smit C, Wasmann RE, Goulooze SC, Hazebroek EJ, Van Dongen EPA, Burgers DMT, et al. A prospective clinical study characterizing the influence of morbid obesity on the pharmacokinetics of gentamicin: towards individualized dosing in obese patients. Clin Pharmacokinet. 2019;58(10):1333–43.PubMedPubMedCentralCrossRef
39.
go back to reference Crass RL, Pai MP. Optimizing estimated glomerular filtration rate to support adult to pediatric pharmacokinetic bridging studies in patients with cystic fibrosis. Clin Pharmacokinet. 2019;58(10):1323–32.PubMedPubMedCentralCrossRef Crass RL, Pai MP. Optimizing estimated glomerular filtration rate to support adult to pediatric pharmacokinetic bridging studies in patients with cystic fibrosis. Clin Pharmacokinet. 2019;58(10):1323–32.PubMedPubMedCentralCrossRef
40.
go back to reference Frymoyer A, Hersh AL, El-Komy MH, Gaskari S, Su F, Drover DR, et al. Association between vancomycin trough concentration and area under the concentration-time curve in neonates. Antimicrob Agents Chemother. 2014;58(11):6454–61.PubMedPubMedCentralCrossRef Frymoyer A, Hersh AL, El-Komy MH, Gaskari S, Su F, Drover DR, et al. Association between vancomycin trough concentration and area under the concentration-time curve in neonates. Antimicrob Agents Chemother. 2014;58(11):6454–61.PubMedPubMedCentralCrossRef
41.
go back to reference Bauer RJ. NONMEM tutorial part II: estimation methods and advanced examples. CPT Pharmacomet Syst Pharmacol. 2019;8(8):538–56.CrossRef Bauer RJ. NONMEM tutorial part II: estimation methods and advanced examples. CPT Pharmacomet Syst Pharmacol. 2019;8(8):538–56.CrossRef
42.
go back to reference Maitre PO, Ausems ME, Vozeh S, Stanski DR. Evaluating the accuracy of using population pharmacokinetic data to predict plasma concentrations of alfentanil. Anesthesiology. 1988;68(1):59–67.PubMedCrossRef Maitre PO, Ausems ME, Vozeh S, Stanski DR. Evaluating the accuracy of using population pharmacokinetic data to predict plasma concentrations of alfentanil. Anesthesiology. 1988;68(1):59–67.PubMedCrossRef
43.
go back to reference Hara M, Masui K, Eleveld DJ, Struys MMRF, Uchida O. Predictive performance of eleven pharmacokinetic models for propofol infusion in children for long-duration anaesthesia. Br J Anaesth. 2017;118(3):415–23.PubMedCrossRef Hara M, Masui K, Eleveld DJ, Struys MMRF, Uchida O. Predictive performance of eleven pharmacokinetic models for propofol infusion in children for long-duration anaesthesia. Br J Anaesth. 2017;118(3):415–23.PubMedCrossRef
44.
go back to reference Miyabe-Nishiwaki T, Masui K, Kaneko A, Nishiwaki K, Nishio T, Kanazawa H. Evaluation of the predictive performance of a pharmacokinetic model for propofol in Japanese macaques (Macaca fuscata fuscata). J Vet Pharmacol Ther. 2013;36(2):169–73.PubMedCrossRef Miyabe-Nishiwaki T, Masui K, Kaneko A, Nishiwaki K, Nishio T, Kanazawa H. Evaluation of the predictive performance of a pharmacokinetic model for propofol in Japanese macaques (Macaca fuscata fuscata). J Vet Pharmacol Ther. 2013;36(2):169–73.PubMedCrossRef
45.
go back to reference Comets E, Brendel K, Mentré F. Computing normalised prediction distribution errors to evaluate nonlinear mixed-effect models: the npde add-on package for R. Comput Methods Programs Biomed. 2008;90(2):154–66.PubMedCrossRef Comets E, Brendel K, Mentré F. Computing normalised prediction distribution errors to evaluate nonlinear mixed-effect models: the npde add-on package for R. Comput Methods Programs Biomed. 2008;90(2):154–66.PubMedCrossRef
46.
go back to reference Hughes JH, Tong DMH, Faldasz JD, Frymoyer A, Keizer RJ. Evaluation of neonatal and paediatric vancomycin pharmacokinetic models and the impact of maturation and serum creatinine covariates in a large multicentre data set. Clin Pharmacokinet. 2023;62(1):67–76.PubMedCrossRef Hughes JH, Tong DMH, Faldasz JD, Frymoyer A, Keizer RJ. Evaluation of neonatal and paediatric vancomycin pharmacokinetic models and the impact of maturation and serum creatinine covariates in a large multicentre data set. Clin Pharmacokinet. 2023;62(1):67–76.PubMedCrossRef
47.
go back to reference Heus A, Uster DW, Grootaert V, Vermeulen N, Somers A, In’t Veld DH, et al. Model-informed precision dosing of vancomycin via continuous infusion: a clinical fit-for-purpose evaluation of published PK models. Int J Antimicrob Agents. 2022;59(5): 106579.PubMedCrossRef Heus A, Uster DW, Grootaert V, Vermeulen N, Somers A, In’t Veld DH, et al. Model-informed precision dosing of vancomycin via continuous infusion: a clinical fit-for-purpose evaluation of published PK models. Int J Antimicrob Agents. 2022;59(5): 106579.PubMedCrossRef
48.
go back to reference Colin PJ, Allegaert K, Thomson AH, Touw DJ, Dolton M, de Hoog M, et al. Vancomycin pharmacokinetics throughout life: results from a pooled population analysis and evaluation of current dosing recommendations. Clin Pharmacokinet. 2019;58(6):767–80.PubMedCrossRef Colin PJ, Allegaert K, Thomson AH, Touw DJ, Dolton M, de Hoog M, et al. Vancomycin pharmacokinetics throughout life: results from a pooled population analysis and evaluation of current dosing recommendations. Clin Pharmacokinet. 2019;58(6):767–80.PubMedCrossRef
49.
go back to reference Cunio CB, Uster DW, Carland JE, Buscher H, Liu Z, Brett J et al. Towards precision dosing of vancomycin in critically ill patients: an evaluation of the predictive performance of pharmacometric models in ICU patients. Clin Microbiol Infect. 2021;27(5):783.e7–783.e14 Cunio CB, Uster DW, Carland JE, Buscher H, Liu Z, Brett J et al. Towards precision dosing of vancomycin in critically ill patients: an evaluation of the predictive performance of pharmacometric models in ICU patients. Clin Microbiol Infect. 2021;27(5):783.e7–783.e14
50.
go back to reference Nguyen TH, Mouksassi MS, Holford N, Al-Huniti N, Freedman I, Hooker AC, et al. Model evaluation of continuous data pharmacometric models: metrics and graphics. CPT Pharmacomet Syst Pharmacol. 2017;6(2):87–109.CrossRef Nguyen TH, Mouksassi MS, Holford N, Al-Huniti N, Freedman I, Hooker AC, et al. Model evaluation of continuous data pharmacometric models: metrics and graphics. CPT Pharmacomet Syst Pharmacol. 2017;6(2):87–109.CrossRef
51.
go back to reference Bensken WP, Pieracci FM, Ho VP. Basic introduction to statistics in medicine, part 1: describing data. Surg Infect (Larchmt). 2021;22(6):590–6.PubMedCrossRef Bensken WP, Pieracci FM, Ho VP. Basic introduction to statistics in medicine, part 1: describing data. Surg Infect (Larchmt). 2021;22(6):590–6.PubMedCrossRef
52.
go back to reference Hsu LF. A survey of population pharmacokinetic reports submitted to the USFDA: an analysis of common issues in NDA and BLA from 2012 to 2021. Clin Pharmacokinet. 2022;61(12):1697–703.PubMedCrossRef Hsu LF. A survey of population pharmacokinetic reports submitted to the USFDA: an analysis of common issues in NDA and BLA from 2012 to 2021. Clin Pharmacokinet. 2022;61(12):1697–703.PubMedCrossRef
53.
Metadata
Title
Does Sample Size, Sampling Strategy, or Handling of Concentrations Below the Lower Limit of Quantification Matter When Externally Evaluating Population Pharmacokinetic Models?
Authors
Mehdi El Hassani
Uwe Liebchen
Amélie Marsot
Publication date
05-05-2024
Publisher
Springer International Publishing
Published in
European Journal of Drug Metabolism and Pharmacokinetics / Issue 4/2024
Print ISSN: 0378-7966
Electronic ISSN: 2107-0180
DOI
https://doi.org/10.1007/s13318-024-00897-1