Seiichi Hayato

Publications (2)5.78 Total impact

• Article: Pharmacokinetic and pharmacodynamic profiling of cefepime in plasma and peritoneal fluid of abdominal surgery patients.

  Kazuro Ikawa, Norifumi Morikawa, Seiichi Hayato, Kayo Ikeda, Hiroki Ohge, Taijiro Sueda
  [show abstract] [hide abstract]
  ABSTRACT: This study was conducted to characterise the pharmacokinetics and pharmacodynamics of cefepime in plasma and peritoneal fluid (PF). One gram of cefepime was administered to eight laparotomy patients and plasma and PF samples were collected at the end of 0.5 h infusion and every hour for 6 h. Drug concentrations were determined, analysed by population pharmacokinetic modelling and used for a Monte Carlo simulation with minimum inhibitory concentration (MIC) data. The maximum concentration in PF was two-thirds of the value in plasma; however, the concentrations were higher in PF than in plasma at 0.68 h post dose. The probabilities of attaining the pharmacodynamic target (65% of the time above the MIC) were 92-99% in plasma (90% fraction unbound) and 93-100% in PF against Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae with a regimen of 1 g every 12 h. However, 1 g every 8 h or 2 g every 12 h was required for values of 94-95% in plasma and 95-96% in PF against Pseudomonas aeruginosa. These results demonstrate that the pharmacodynamic exposures in PF were almost identical to those estimated from plasma data and provided a pharmacokinetic/pharmacodynamic rationale for the dosing regimen for surgical intra-abdominal infections.
  International Journal of Antimicrobial Agents 10/2007; 30(3):270-3. · 4.13 Impact Factor
• Article: Pharmacokinetic and pharmacodynamic properties of lafutidine after postprandial oral administration in healthy subjects: comparison with famotidine.

  Kazuro Ikawa, Tomohiko Shimatani, Seiichi Hayato, Norifumi Morikawa, Susumu Tazuma
  [show abstract] [hide abstract]
  ABSTRACT: Lafutidine, a histamine H(2)-receptor antagonist, inhibits gastric acid secretion during the daytime, however, the relationship between the plasma concentration and the drug response remains unclear. The aim of this study was to compare the pharmacokinetic and pharmacodynamic properties of lafutidine and famotidine following postprandial oral administration. After a lafutidine tablet (10 mg), famotidine tablet (20 mg), or water only (control) was administered, blood samples were taken and intragastric pH was measured. The plasma concentrations of lafutidine and famotidine were determined by HPLC, and the median intragastric pH values per 30 min were used as the degrees of gastric acid suppression. Data were analyzed based on a one-compartment pharmacokinetic model and a sigmoid E(max) pharmacodynamic model. Lafutidine plasma concentrations rapidly increased after administration; famotidine required some time to increase the plasma concentrations, requiring an absorption lag time in the pharmacokinetic model. Between the plasma concentration and DeltapH (the difference in intragastric pH by the drug vs. control), lafutidine showed an anticlockwise hysteresis loop which indicated equilibration delay between the plasma concentration and effect site, requiring an effect site compartment in the pharmacodynamic model; famotidine showed more parallel relationship. These results indicated that the pharmacokinetic and pharmacodynamic properties of lafutidine after postprandial oral administration were different from those of famotidine at least 4.5 h after dosing.
  Biological & Pharmaceutical Bulletin 06/2007; 30(5):1003-6. · 1.66 Impact Factor