Teicoplanin physiologically based pharmacokinetic modeling offers a quantitative assessment of a theoretical influence of serum albumin and renal function on its disposition
| Autor: | Chie Emoto, Trevor N. Johnson, Tsuyoshi Fukuda, Takaaki Yamada, Hiroshi Yamazaki |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Physiologically based pharmacokinetic modelling Metabolic Clearance Rate Cmax Serum albumin Renal function Pharmacology Models Biological 030226 pharmacology & pharmacy Loading dose White People 03 medical and health sciences 0302 clinical medicine Asian People Pharmacokinetics Humans Medicine Computer Simulation Pharmacology (medical) Renal Insufficiency 030212 general & internal medicine Serum Albumin Aged biology Maintenance dose business.industry Teicoplanin Patient Acuity General Medicine Middle Aged Anti-Bacterial Agents Area Under Curve biology.protein Female business Glomerular Filtration Rate medicine.drug |
| Zdroj: | European Journal of Clinical Pharmacology. 77:1157-1168 |
| ISSN: | 1432-1041 0031-6970 |
| DOI: | 10.1007/s00228-021-03098-w |
| Popis: | Variability in teicoplanin pharmacokinetics has been explained by multiple factors such as body weight, renal function, and serum albumin level. To improve mechanistic understanding of the causes of variability, a physiologically based pharmacokinetic (PBPK) model can be used as a systematic platform. In this study, a PBPK model of teicoplanin was developed to quantitatively assess the effects of physiological changes due to disease status using virtual populations. Predictive performance of the models was evaluated by comparing simulated and observed concentration-time profiles of teicoplanin. Subsequently, sensitivity analyses were conducted to identify potential factors contributing to individual differences in teicoplanin PK. The developed PBPK model generated concentration-time profiles that were comparable to clinical observations in healthy adults, including Caucasians and Japanese, and after single-dose and multiple-dose administration. The predicted PK parameters (i.e., Cmax, AUC, clearance) were within a two-fold range of the observed data in patients with renal impairments as well as healthy adults. Changes in total and unbound teicoplanin concentrations at 72 h, after various dosing regimens (tested 4-14 mg/kg q12h for three doses as a loading dose and then 4-14 mg/kg daily as a maintenance dose), were sensitive to renal function and serum albumin concentrations. The PBPK model of teicoplanin provides mechanistic insight into the factors altering its disposition and allows assessments of the theoretical and quantitative impact of individual changes in physiological parameters on its PK even when an actual assessment with adequate sample sizes of patients is challenging. |
| Databáze: | OpenAIRE |
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