Sadahiro Abe

Publications (2)4.09 Total impact

• Article: Low-molecular-weight heparin pharmacokinetics: a dual absorption model approach.

  Sadahiro Abe, Koji Chiba, Toshio Suwa
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  ABSTRACT: Objective: The aim of this study was to develop a novel population pharmacokinetic (PPK) model of dalteparin after subcutaneous (s.c.) injection, to describe the impact of the "flip-flop" phenomenon and to demonstrate any ethnic difference between Asian and Caucasian subjects. Materials and methods: The PPK model was constructed based on data collected from Asian (Japanese) and Caucasian (French) subjects with a total of 931 plasma anti-Xa activity measurements. After s.c. injection, the apparent elimination half-life of the dalteparin was about 4 hours, longer than that reported after intravenous (i.v.) injection, indicating a "flip-flop" phenomenon. In addition, following the mono-exponential decline profile after s.c. injection, a longer secondary phase was apparently observed in 70% of subjects. To investigate the phenomenon, we applied a dual absorption model including fast first-order and slow zero-order inputs as the structural model. Results: The PPK model for s.c. injection provided the half-life consistent with that of i.v. injection and could account for the observed bi-phasic profile. Body weight and gender for clearance and body weight for volume of distribution were identified as covariates. Due to lower body weight in Asian subjects, an ethnic difference might occur but it would not be reflected by per kg body weight injection. Conclusions: Dalteparin PK profiles after s.c. injection were described reasonably by the novel PPK model based on flip-flop pharmacokinetics and a dual absorption process.
  International journal of clinical pharmacology and therapeutics 04/2013; · 1.18 Impact Factor
• Article: Population pharmacokinetic analysis of linezolid in patients with infectious disease: application to lower body weight and elderly patients.

  Sadahiro Abe, Koji Chiba, Brenda Cirincione, Thaddeus H Grasela, Kaori Ito, Toshio Suwa
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  ABSTRACT: Linezolid (Zyvox), belonging to oxazolidinone antibiotics, is commonly used for the treatment of patients infected with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Although linezolid has been approved worldwide, the Japanese pharmacokinetic (PK) profile has not been characterized in detail. The objective of this study is to develop a population PK model for linezolid that can be applied to a Japanese population. This population PK model was established based on the 1 Japanese phase III and 4 Caucasian phase II/III studies. A total of 2539 linezolid plasma concentration measurements from 455 patients, aged 18 to 98 years and body weight 30 to 190.5 kg, were used for the analysis. The data were analyzed using nonlinear mixed effects modeling. Body weight (BW), age, ethnicity, and gender were investigated as covariates. The final model was validated by the bootstrap technique. The PK profiles of linezolid were described with a 1-compartment PK model with first-order absorption and first-order elimination. In the final population PK model, BW and age were influential covariates on clearance, and the distribution volume was affected by BW. The present population PK model of linezolid described well the PK profiles in Japanese patients who have lower BW and are relatively older compared with those in the United States/European Union.
  The Journal of Clinical Pharmacology 07/2009; 49(9):1071-8. · 2.91 Impact Factor