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Journal of Infection and Chemotherapy

, Volume 2, Issue 4, pp 271–279 | Cite as

Phase I clinical studies of S-1090: Safety and pharmacokinetics

  • Mitsuyoshi Nakashima
  • Takayoshi Oguma
  • Yasuo Kimura
  • Shimaru Sasaki
  • Yuji Sendo
  • Hiromichi Imoto
Note

Abstract

S-1090, an oral cephem antibiotic, was given to healthy male volunteers in single (10 to 400 mg) and multiple (200 mg, twice a day) doses. There were no abnormalities in subjective and objective signs, or physical findings, in any subjects. The intestinal and oropharyngeal bacterial flora were not significantly affected by S-1090. These results suggest that S-1090 is a safe and well-tolerated drug. Food intake increased the absorption of S-1090, but did not affect its half-life. The plasma concentration increased with increasing doses, but at a rate less than proportional to the dose, in the single-dose studies. S-1090 was eliminated with a half-life of 2 to 3 hours after oral administration under nonfasting conditions, independent of dose. Urinary recovery rate decreased with increasing doses. The maximum plasma concentration, half-life, and area under the concentration-time curve at the dose of 100 mg in nonfasting conditions were 3.78 μg/ml, 2.77 hours, and 25.51 μg·h/mL, respectively. S-1090 may be absorbed by both unsaturable passive and saturable active transport systems. During multiple dosing, the extent of absorption decreased slightly, but steady state was achieved within several days without changes in half-life. S-1090 binds to serum protein constantly, at a very high 97%, which might cause the long half-life of this drug. The high plasma concentration and long half-life of S-1090 are favorable for clinical use.

Key words

S-1090 oral cephem antibiotic phase I clinical studies pharmacokinetics 

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Copyright information

© Japan Society of Chemotherapy 1996

Authors and Affiliations

  • Mitsuyoshi Nakashima
    • 1
  • Takayoshi Oguma
    • 2
  • Yasuo Kimura
    • 2
  • Shimaru Sasaki
    • 2
  • Yuji Sendo
    • 2
  • Hiromichi Imoto
    • 2
  1. 1.Department of PharmacologyHamamatsu University School of MedicineHamamatsuJapan
  2. 2.Shionogi Research LaboratoriesShionogi and Co LtdOsakaJapan

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