Application of a physiologically based pharmacokinetic model for the prediction of mirabegron plasma concentrations in a population with severe renal impairment

2019 ◽  
Vol 40 (5-6) ◽  
pp. 176-187
Author(s):  
Kentaro Konishi ◽  
Tsuyoshi Minematsu ◽  
Yasuhisa Nagasaka ◽  
Kenji Tabata
Keyword(s):  
Renal Impairment ◽  
Pharmacokinetic Model ◽  
Severe Renal Impairment ◽  
Plasma Concentrations ◽  
Physiologically Based Pharmacokinetic Model ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based

scholarly journals Pharmacokinetics of anticoagulant edoxaban in overdose in a Japanese patient transported to hospital

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Koichiro Adachi ◽  
Jumpei Tuchiya ◽  
Satoru Beppu ◽  
Kei Nishiyama ◽  
Makiko Shimizu ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Pharmacokinetic Model ◽  
Medical Center ◽  
Plasma Concentrations ◽  
Elimination Rate ◽  
Physiologically Based Pharmacokinetic Model ◽  
Current Case ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based

Abstract Background The anticoagulant edoxaban is used clinically at doses of 30–60 mg/day; however, we experienced a patient who had taken an overdose of edoxaban of 750 mg. We investigated the pharmacokinetics of edoxaban in this patient by using liquid chromatography–tandem spectrometry to estimate the follow-up period in emergency clinical practice with this medicine. Case presentation The patient was a 57-year-old woman (body weight, 69 kg) who had taken a single oral dose of 750 mg of edoxaban in a suicide attempt. She was emergently admitted to Kyoto Medical Center. The patient’s edoxaban plasma concentrations during ambulance transport (8 h after oral administration) were ~ 4900 ng/ml, and the concentration gradually decreased to ~ 10 ng/mL and to detectable but unmeasurable levels of ~ 1.0 ng/mL at 60 h and 100 h, respectively. The linear range of the relationship between the dose and plasma concentration was assumed to have been exceeded during the first 8 h; however, the measured elimination rate of edoxaban was similar to that visualized curves predicted by a simplified physiologically based pharmacokinetic model previously established. Conclusion Simplified physiologically based pharmacokinetic models for creating visualized curves have proven to be useful not only during drug discovery or chemical risk assessment but also in cases of medical poisoning. We used a physiologically based pharmacokinetic model previously established for edoxaban to predict the pharmacokinetics in the current case. It is hoped that the results of this study, which encompass drug monitoring data in the patient and visualized pharmacokinetic prediction, will serve as an index when setting the treatment and follow-up period in cases of drug overdose for medicines such as edoxaban in emergency clinical practice.

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