Vol.53 No.S-1 July 2005

Pharmacokinetics of doripenem in patients with renal dysfunction

Shinya Uehara¹⁾, Wataru Murao¹⁾, Yuko Seno¹⁾, Eiichi Andoh¹⁾, Kouichi Monden¹⁾, Reiko Kariyama¹⁾, Masaya Tsugawa²⁾, Mitsuyoshi Nakashima³⁾ and Hiromi Kumon¹⁾

¹⁾Department of Urology, Okayama University Graduate School of Medicine and Dentistry,
2-5-1 Shikata-cho, Okayama, Japan
²⁾Department of Urology, Okayama Citizens'Hospital
³⁾Hamamatsu Institute of Clinical Pharmacology & Therapeutics
(Professor Emeritus, Hamamatsu University School of Medicine)

Abstract

We compared pharmacokinetic profiles of doripenem (DRPM) in patients with renal dysfunction to those in healthy volunteers in a Phase I study.
Patients with renal dysfunction were divided into 3 groups based on creatinine clearance (Ccr): mild dysfunction with 50≤Ccr<70 mL/min (Group I, n=4), moderate dysfunction with 30≤Ccr<50 mL/min (Group II, n=6), and severe dysfunction with Ccr<30 mL/min (Group III, n=2). Area under the blood concentration curve (AUC) in healthy volunteers after DRPM administration (250 mg) was 20.26 μg · h/mL, while AUCs in Groups I, II and III were 40.55 μg · h/mL, 48.21 μg · h/mL and 64.31 μg · h/mL. These results indicated that AUC increased with the severity of renal dysfunction. Half-lives were 0.90, 1.98, 2.16, and 3.56 h in healthy volunteers, Group I, Group II, and Group III, and prolonged based on renal dysfunction severity.
Urinary excretion (0-24 h) was 74.5%, 63.9%, 67.3%, and 58.2% in healthy volunteers, Group I, Group II, and Group III, decreasing based on renal dysfunction severity.
No adverse reactions were observed.
Our results suggest that the DRPM dosage and dosing interval should be determined carefully when in administration to patients with renal dysfunction.

Key word

doripenem, renal dysfunction, pharmacokinetic

Received

January 11, 2005

Accepted

March 28, 2005

Jpn. J. Chemother. 53 (S-1): 130-135, 2005