| Autor: |
Frédéric Gaspar, Jean Terrier, Samantha Favre, Pauline Gosselin, Pierre Fontana, Youssef Daali, Camille Lenoir, Caroline Flora Samer, Victoria Rollason, Jean‐Luc Reny, Chantal Csajka, Monia Guidi |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
CPT: Pharmacometrics & Systems Pharmacology, Vol 12, Iss 10, Pp 1541-1552 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2163-8306 |
| DOI: |
10.1002/psp4.13032 |
| Popis: |
Abstract This study aimed to characterize apixaban pharmacokinetics (PKs) and its variability in a real‐world clinical setting of hospitalized patients using a population PK (PopPK) approach. Model‐based simulations helped to identify factors that affect apixaban exposure and their clinical significance. A classic stepwise strategy was applied to determine the best PopPK model for describing typical apixaban PKs in hospitalized patients from the OptimAT study (n = 100) and evaluating the associated variability and influencing factors. Apixaban exposure under specific conditions was assessed using the final model. A two‐compartment model with first‐order absorption and elimination best described the data. The developed PopPK model revealed a major role of renal function and a minor role of P‐glycoprotein phenotypic (P‐gp) activity in explaining apixaban variability. The final model indicated that a patient with stage 4 chronic kidney disease (creatinine clearance [CLcr] = 15–29 mL/min) would have a 45% higher drug exposure than a patient with normal renal function (CLcr >90 mL/min), with a further 12% increase if the patient was also a poor metabolizer of P‐gp. A high interindividual variability in apixaban PKs was observed in a real‐life setting, which was partially explained by renal function and by P‐gp phenotypic activity. Target apixaban concentrations are reached under standard dosage regimens, but overexposure can rapidly occur in the presence of cumulative factors warranting the development of a predictive tool for tailoring apixaban exposure and its clinical utility in at‐risk patients. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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