Vol.53 No.S-1 July 2005
Pharmacokinetic profiles and clinical efficacy of doripenem in surgical infection
1)Wakayama Rosai Hospital, 435 Koya, Wakayama, Japan
2)Keio University School of Medicine
3)Toho University Ohashi Hospital
4)Hiroshima University Hospital (Present: Aki City Hospital)
Abstract
We conducted pharmacokinetic studies to determine the concentrations of doripenem (DRPM), a new carbapenem antibiotic with broad antibacterial activity, in bile and gallbladder tissue (early phase II study) and in peritoneal fluid (phase III study). A late phase II study and a phase III study were also conducted in patients with surgical infection to evaluate the clinical efficacy of DRPM. Results are as follows:
1. Pharmacokinetic profiles
A single 30-minute intravenous infusion of DRPM (250 mg) was administered to ten patients scheduled to undergo cholecystectomy. DRPM concentration in bile was <0.16-15.4 μg/mL and in gall bladder tissue <0.10-1.87 μg/g.
A single 30-minute intravenous infusion of DRPM (250 mg) was administered to five patients who underwent abdominal surgery. Maximum plasma concentration was 10.5-24.4 μg/mL and maximum peritoneal fluid concentration within the same period 2.36-5.17 μg/mL.
2. Clinical efficacy and safety
Late phase II study (48 patients): DRPM was administered at a dose of 250 mg b.i.d., 250 mg t.i.d., or 500 mg b.i.d. for 3 to 14 days in 22 patients with postoperative infection, four with intraabdominal abscess, seven with peritonitis, four with liver abscess, six with cholecystitis, and five with cholangitis. Clinical efficacy was evaluated as "excellent" in 12, "good" in 31, "fair" in two, and "poor" in three, with efficacy of 89.6% (43/48). Bacterial eradication was 61.3% (19/31). Adverse drug reactions (symptoms) occurred in one of 48 (2.1%) and adverse drug reactions (abnormal laboratory findings) in seven of 46 (15.2%).
Phase III study (15 patients): DRPM was administered at a dose of 250 mg b.i.d., 250 mg t.i.d., or 500 mg b.i.d. for 4 to 14 days in seven patients with intraabdominal abscess, two with liver abscess, and six patients with cholecystitis. Clinical efficacy was evaluated as "excellent" in two and "good" in 13, with efficacy of 100%. Bacterial eradication was 54.5% (6/11). Adverse drug reactions (abnormal laboratory findings) occurred in four of 15 (26.7%), with no adverse drug reactions (symptoms) reported in any.
These results suggest that DRPM at a dose of 250 mg b.i.d., 250 mg t.i.d., or 500 mg b.i.d. has a sufficient therapeutic effect on patients with surgical infection.
Key word
doripenem, pharmacokinetics, tissue concentration, surgical site infection, clinical efficacy
Received
January 11, 2005
Accepted
February 17, 2005
Jpn. J. Chemother. 53 (S-1): 260-272, 2005
