Phase I study of doripenem, a new carbapenem antibiotic for injection in healthy volunteers
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Accession number;05A0663317
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| Title;Phase I study of doripenem, a new carbapenem antibiotic for injection in healthy volunteers |
| Author;
NAKASHIMA MITSUYOSHI
(Hamamatsushipitiken)
OGUMA TAKAYOSHI
(Shionogi & Co., Ltd., JPN)
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Journal Title;Japanese Journal of Chemotherapy
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Journal Code:F0608A
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ISSN:1340-7007
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VOL.53;NO.Supplement 1;PAGE.104-123(2005)
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| Figure&Table&Reference;FIG.13, TBL.21, REF.5 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;To evaluate the safety and pharmacokinetic profiles of doripenem (DRPM), a new carbapenem antibiotic for injection, we conducted a phase I study in 46 healthy male volunteers. DRPM was administered as follows: 1) a single infusion at a dose of 125-1,000 mg, 2) an infusion of 500 mg twice a day (1,000 mg/day) for 6 days (11 repeated infusions), 3) an infusion of 1,000 mg twice a day (2,000 mg/day) for 6 days (11 repeated infusions), and 4) an infusion of 500 mg 3 times a day (1,500 mg/day) for 1 day (3 repeated infusions). In terms of safety, no abnormalities were found in the single-dose study. No abnormalities were found in electroencephalography or physical examination. In repeated dose studies, mild subjective symptoms/objective observations and slight changes in laboratory values were observed, although none were clinically relevant. In the single-dose study, Cmax and AUC of DRPM increased in proportion to the dose, showing linearity between pharmacokinetic profiles and the DRPM dose. The plasma half-life of DRPM was approximately 1 hour at any dose. Within 24 hours of administration, approximately 75% of DRPM was excreted unchanged in urine. Results from the repeated-dose study showed that DRPM pharmacokinetic profiles were not affected by a repeated dose. In addition, DRPM was found not to be accumulated. The mean serum protein binding ratio was 5.4-15.2%. Intestinal flora was slightly affected by DRPM administration. This study showed that DRPM administration is safe up to a dose of 1,000 mg, and pharmacokinetic profiles are not affected by a repeated dose, with no DRPM accumulation. (author abst.) |
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