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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
A Model-Informed Method for the Purpose of Precision Dosing of Isoniazid in Pulmonary Tuberculosis
Clinical Pharmacokinetics, Volume 60, No. 7, Year 2021
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Description
Background and Objective: This study aimed to develop and evaluate a population pharmacokinetic model and limited sampling strategy for isoniazid to be used in model-based therapeutic drug monitoring. Methods: A population pharmacokinetic model was developed based on isoniazid and acetyl-isoniazid pharmacokinetic data from seven studies with in total 466 patients from three continents. Three limited sampling strategies were tested based on the available sampling times in the dataset and practical considerations. The tested limited sampling strategies sampled at 2, 4, and 6 h, 2 and 4 h, and 2 h after dosing. The model-predicted area under the concentration–time curve from 0 to 24 h (AUC24) and the peak concentration from the limited sampling strategies were compared to predictions using the full pharmacokinetic curve. Bias and precision were assessed using the mean error (ME) and the root mean square error (RMSE), both expressed as a percentage of the mean model-predicted AUC24 or peak concentration on the full pharmacokinetic curve. Results: Performance of the developed model was acceptable and the uncertainty in parameter estimations was generally low (the highest relative standard error was 39% coefficient of variation). The limited sampling strategy with sampling at 2 and 4 h was determined as most suitable with an ME of 1.1% and RMSE of 23.4% for AUC24 prediction, and ME of 2.7% and RMSE of 23.8% for peak concentration prediction. For the performance of this strategy, it is important that data on both isoniazid and acetyl-isoniazid are used. If only data on isoniazid are available, a limited sampling strategy using 2, 4, and 6 h can be employed with an ME of 1.7% and RMSE of 20.9% for AUC24 prediction, and ME of 1.2% and RMSE of 23.8% for peak concentration prediction. Conclusions: A model-based therapeutic drug monitoring strategy for personalized dosing of isoniazid using sampling at 2 and 4 h after dosing was successfully developed. Prospective evaluation of this strategy will show how it performs in a clinical therapeutic drug monitoring setting. © 2021, The Author(s).
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC8249295/bin/40262_2020_971_MOESM1_ESM.pdf
Authors & Co-Authors
van Beek, Stijn W.
Netherlands, Nijmegen
Radboud Universiteit
ter Heine, Rob
Netherlands, Nijmegen
Radboud Universiteit
Alffenaar, Jan Willem C.
Australia, Sydney
The University of Sydney
Australia, Sydney
Westmead Hospital
Magis-Escurra, Cécile
Netherlands, Nijmegen
Radboud University Medical Center
Aarnoutse, Rob Edward
Netherlands, Nijmegen
Radboud Universiteit
Svensson, Elin M.
Netherlands, Nijmegen
Radboud Universiteit
Sweden, Uppsala
Uppsala Universitet
Boeree, Martin Johan
Unknown Affiliation
Burhan, Erlina A.
Unknown Affiliation
Dawson, Rodney
Unknown Affiliation
Diacon, Andreas Henri
Unknown Affiliation
Gillespie, Stephen H.
Unknown Affiliation
Mtabho, Charles M.
Unknown Affiliation
Ntingiya, Nyanda E.
Unknown Affiliation
Heinrich, Norbert
Unknown Affiliation
Hoefsloot, Wouter
Unknown Affiliation
Höelscher, Michael
Unknown Affiliation
Kibiki, Gibson S.
Unknown Affiliation
Reither, Klaus
Unknown Affiliation
Sanne, Ian
Unknown Affiliation
Semvua, Hadija Hamis
Unknown Affiliation
Tostmann, Alma
Unknown Affiliation
Statistics
Citations: 5
Authors: 21
Affiliations: 5
Identifiers
Doi:
10.1007/s40262-020-00971-2
ISSN:
03125963
Study Design
Cross Sectional Study
Cohort Study