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Machine Learning an...
Machine Learning and Pharmacometrics for Prediction of Pharmacokinetic Data : Differences, Similarities and Challenges Illustrated with Rifampicin
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- Keutzer, Lina (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- You, Huifang (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Farnoud, Ali (author)
- Helmholtz Munich, Computat Hlth Ctr, D-85764 Neuherberg, Germany.
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- Nyberg, Joakim, 1978- (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Wicha, Sebastian G. (author)
- Univ Hamburg, Inst Pharm, Dept Clin Pharm, D-20146 Hamburg, Germany.
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- Maher-Edwards, Gareth (author)
- GlaxoSmithKline, Res Clin Pharmacol Modelling & Simulat, London TW8 9GS, England.
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- Vlasakakis, Georgios (author)
- GlaxoSmithKline, Res Clin Pharmacol Modelling & Simulat, London TW8 9GS, England.
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- Moghaddam, Gita Khalili (author)
- GlaxoSmithKline, Res Clin Pharmacol Modelling & Simulat, London TW8 9GS, England.;Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0QQ, England.
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- Svensson, Elin, 1985- (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Institutionen för farmaci,Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, NL-6525 EZ Nijmegen, Netherlands.
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- Menden, Michael P. (author)
- Helmholtz Munich, Computat Hlth Ctr, D-85764 Neuherberg, Germany.;Ludwig Maximilian Univ Munich, Dept Biol, D-82152 Planegg Martinsried, Germany.;German Ctr Diabet Res DZD eV, D-85764 Neuherberg, Germany.
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- Simonsson, Ulrika S. H., Professor (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Institutionen för farmaci
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(creator_code:org_t)
- 2022-07-22
- 2022
- English.
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In: Pharmaceutics. - : MDPI. - 1999-4923. ; 14:8
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Abstract
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- Pharmacometrics (PM) and machine learning (ML) are both valuable for drug development to characterize pharmacokinetics (PK) and pharmacodynamics (PD). Pharmacokinetic/pharmacodynamic (PKPD) analysis using PM provides mechanistic insight into biological processes but is time- and labor-intensive. In contrast, ML models are much quicker trained, but offer less mechanistic insights. The opportunity of using ML predictions of drug PK as input for a PKPD model could strongly accelerate analysis efforts. Here exemplified by rifampicin, a widely used antibiotic, we explore the ability of different ML algorithms to predict drug PK. Based on simulated data, we trained linear regressions (LASSO), Gradient Boosting Machines, XGBoost and Random Forest to predict the plasma concentration-time series and rifampicin area under the concentration-versus-time curve from 0-24 h (AUC(0-24h)) after repeated dosing. XGBoost performed best for prediction of the entire PK series (R-2: 0.84, root mean square error (RMSE): 6.9 mg/L, mean absolute error (MAE): 4.0 mg/L) for the scenario with the largest data size. For AUC(0-24h) prediction, LASSO showed the highest performance (R-2: 0.97, RMSE: 29.1 h center dot mg/L, MAE: 18.8 h center dot mg/L). Increasing the number of plasma concentrations per patient (0, 2 or 6 concentrations per occasion) improved model performance. For example, for AUC(0-24h) prediction using LASSO, the R-2 was 0.41, 0.69 and 0.97 when using predictors only (no plasma concentrations), 2 or 6 plasma concentrations per occasion as input, respectively. Run times for the ML models ranged from 1.0 s to 8 min, while the run time for the PM model was more than 3 h. Furthermore, building a PM model is more time- and labor-intensive compared with ML. ML predictions of drug PK could thus be used as input into a PKPD model, enabling time-efficient analysis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- machine learning
- pharmacometrics
- population pharmacokinetics
- rifampicin
- pharmacokinetics
- simulation
- feature selection
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Keutzer, Lina
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You, Huifang
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Farnoud, Ali
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Nyberg, Joakim, ...
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Wicha, Sebastian ...
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Maher-Edwards, G ...
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Vlasakakis, Geor ...
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Moghaddam, Gita ...
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Svensson, Elin, ...
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Menden, Michael ...
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Simonsson, Ulrik ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
- Articles in the publication
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Pharmaceutics
- By the university
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Uppsala University