Vol.53 No.S-1 July 2005
A study of distribution of doripenem in otolaryngologic tissues and clinical relevance in otolaryngologic infection
1)Department of Otorhinolaryngology, Nagoya City University Medical School,
1-1-4 Hiyori-cho, Chikusa-ku, Nagoya, Aichi, Japan
2)Department of Otorhinolaryngology, Second Affiliated Hospital, Fujita Health University
3)Department of Otorhinolaryngology, Kamo Hospital
Abstract
We studied the distribution of doripenem (DRPM), a new carbapenem antibiotic for injection, in otolaryngologic tissue. To evaluate the efficacy and safety of DRPM, we also conducted an open-label clinical trial in patients with moderate to severe otitis media and peritonsillar abscess (including severe lacunar tonsillitis and peritonsillitis).
After an infusion of DRPM (250 mg), the concentration in removed tissues (palatine tonsil and mucosa of middle ear), and the ratio to plasma concentration in the same period were 0.27-2.58 μg/g and 6.1-33.2% (60-155 minutes) in the palatine tonsil and 0.26-6.09 μg/g and 2.7-42.9% (60-90 minutes) in the mucosa of the middle ear.
DRPM was administered at a dose of 250 mg b.i.d., 250 mg t.i.d., or 500 mg b.i.d. for seven days. In otitis media, DRPM was "highly effective" in four patients and "effective" and "slightly effective" in one each. In peritonsillar abscess, DRPM was "highly effective" in four patients and "effective" in two patients. After DRPM infusion at the clinically recommended dose of 250 mg, the concentration of DRPM in middle ear discharge and the ratio to plasma concentration in patients with otitis media were 0.32-0.72 μg/mL and 4.2-18.8% (75-170 minutes). Microbiological response was studied in nine patients-five with otitis media and four with peritonsillar abscess. We found it to be "eradicated" in four patients and "decreased" in one with otitis media; while in peritonsillar abscess, it was found to be "eradicated" in all the four. In safety, the incidence of adverse drug reactions (abnormal symptoms) was 6.7% (1/15) and that of adverse drug reactions (abnormal laboratory findings) 26.7% (4/15), none of which were serious.
These results suggest that DRPM is distributed well in otolaryngologic tissues and that DRPM administration at a dose of 250 mg b.i.d. or t.i.d., or at a dose of 500 mg b.i.d. is clinical by useful in otolaryngologic infection, with a wide antimicrobial spectrum and strong antimicrobial activity against gram-positive bacteria, gram-negative bacteria, and anaerobes.
Key word
doripenem, tissue concentration, otolaryngological infection, clinical evaluation
Received
January 11, 2005
Accepted
March 15, 2005
Jpn. J. Chemother. 53 (S-1): 293-302, 2005
