Sökning: WFRF:(Karlsson Mats O) >
Population Pharmaco...
Population Pharmacokinetics of Edoxaban in Patients with Non-Valvular Atrial Fibrillation in the ENGAGE AF-TIMI 48 Study, a Phase III Clinical Trial
-
- Krekels, Elke H. J. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,LACDR Div Pharmacol, POB 9502, NL-2300 RA Leiden, Netherlands.
-
- Niebecker, Ronald (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
-
- Karlsson, Mats O. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
-
visa fler...
-
- Miller, Raymond (författare)
- Daiichi Sankyo Pharma Dev, Edison, NJ USA.
-
- Shimizu, Takako (författare)
- Daiichi Sankyo Co Ltd, Tokyo, Japan.
-
- Karlsson, Kristin E. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
-
- Ruff, Christian T. (författare)
- Brigham & Womens Hosp, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.
-
- Simonsson, Ulrika S. H. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
-
- Jönsson, Siv (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
-
visa färre...
-
(creator_code:org_t)
- 2016-03-07
- 2016
- Engelska.
-
Ingår i: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 55:9, s. 1079-1090
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Introduction: Edoxaban is a novel factor Xa inhibitor. This study characterizes the population pharmacokinetics of edoxaban in patients with non-valvular atrial fibrillation (NVAF) included in the phase III ENGAGE AF-TIMI 48 study, evaluates covariates for the dose-exposure relationship in this population, and assesses the impact of protocol-specified dose reductions on exposure using simulations.Methods: Model development was performed using NONMEMA (R) and based on sparse data from the ENGAGE AF-TIMI 48 study augmented with dense data from 13 phase I studies to inform and stabilize the model. The influence of body weight (WT), creatinine clearance (CLCR), concomitant P-glycoprotein (P-gp) inhibitors, age, sex, race, and NVAF on pharmacokinetic parameters was evaluated based on statistical significance and clinical relevance.Results: A two-compartment model with first-order elimination and first-order absorption after an absorption lag-time best described the data. Apparent volume and clearance terms increased with increasing WT. Apparent renal clearance increased with increasing CLCR. Apparent non-renal, renal, and inter-compartmental clearance terms differed between phase I volunteers and NVAF patients. Asian patients were found to have increased apparent central volume of distribution, bioavailability, and total apparent clearance. Concomitant P-gp inhibitors increased the bioavailability statistically significantly, but this did not reach clinical relevance.Conclusion: Edoxaban disposition and the variability in this disposition, including influence of covariates, after oral administration were adequately characterized in patients with NVAF. The 50 % dose reduction in patients with low WT (aecurrency sign60 kg), moderate renal impairment (CLCR aecurrency sign50 mL/min), or concomitant P-gp inhibitors led to 30 % lower exposure than in the other patients.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas