دورية أكاديمية
Proteomics-informed prediction of rosuvastatin plasma profiles in patients with a wide range of body weight.
| العنوان: | Proteomics-informed prediction of rosuvastatin plasma profiles in patients with a wide range of body weight. |
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| المؤلفون: | Wegler, C., Prieto Garcia, L., Klinting, S., Robertsen, I., Wiśniewski, J., Hjelmesaeth, J., Asberg, A., Jansson-Lofmark, R., Andersson, T., Artursson, P. |
| المصدر: | Clinical pharmacology and therapeutics |
| سنة النشر: | 2021 |
| المجموعة: | Max Planck Society: MPG.PuRe |
| الوصف: | Rosuvastatin is a frequently used probe to study transporter-mediated hepatic uptake. Pharmacokinetic models have therefore been developed to predict transporter impact on rosuvastatin disposition in vivo. However, the inter-individual differences in transporter concentrations were not considered in these models, and the predicted transporter impact was compared with historical in vivo data. In this study, we investigated the influence of inter-individual transporter concentrations on the hepatic uptake clearance of rosuvastatin in 54 patients covering a wide range of body weight. The 54 patients were given an oral dose of rosuvastatin the day before undergoing gastric bypass or cholecystectomy, and pharmacokinetic parameters were established from each patient's individual time-concentration profiles. Liver biopsies were sampled from each patient and their individual hepatic transporter concentrations were quantified. We combined the transporter concentrations with in vitro uptake kinetics determined in HEK293-transfected cells, and developed a semi-mechanistic model with a bottom-up approach to predict the plasma concentration profiles of the single dose of rosuvastatin in each patient. The predicted pharmacokinetic parameters were evaluated against the measured in vivo plasma pharmacokinetics from the same 54 patients. The developed model predicted the rosuvastatin pharmacokinetics within two-fold error for rosuvastatin AUC (78% of the patients; AFE: 0.96), Cmax (76%; AFE: 1.05), and t1/2 (98%; AFE: 0.89), and captured differences in the rosuvastatin pharmacokinetics in patients with the OATP1B1 521T |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf; application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
| اللغة: | English |
| العلاقة: | http://hdl.handle.net/21.11116/0000-0007-DF8E-FTest; http://hdl.handle.net/21.11116/0000-0007-DF90-BTest; http://hdl.handle.net/21.11116/0000-0007-DF91-ATest; http://hdl.handle.net/21.11116/0000-0007-DF92-9Test |
| الإتاحة: | https://doi.org/10.1002/cpt.2056Test http://hdl.handle.net/21.11116/0000-0007-DF8E-FTest http://hdl.handle.net/21.11116/0000-0007-DF90-BTest http://hdl.handle.net/21.11116/0000-0007-DF91-ATest http://hdl.handle.net/21.11116/0000-0007-DF92-9Test |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by-nc/4.0Test/ |
| رقم الانضمام: | edsbas.9108149D |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |