Vol.53 No.5 May 2005
Adjustment of cefepime dosage in patients with renal impairment
Early Development, PRI Japan, Bristol-Myers K. K.,
Shinjuku i-Land Tower, 6-5-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo, Japan
Abstract
We studied dose regimens of cefepime (CFPM) in patients with renal impairment using population pharmacokinetic (PPK) modeling. PPK analysis incorporated body weight (BW) and creatinine clearance (Ccr) as covariates and was used to predict serum concentration-time profiles and pharmacokinetic (PK) parameters after 30-minute intravenous infusion at 0.5-2 g of CFPM once (QD) or twice (BID) a day in patients with Ccr from 5 to 50 mL/min and BW between 40 kg and 90 kg. For late-stage renal failure patients undergoing hemodialysis, PK profiles of CFPM after a 1 g loading dose followed by 0.5 g QD dose were estimated in patients with Ccr of 5 mL/min by a PPK model modified with hemodialysis clearance. Hemodialysis was modeled as three times a week just before CFPM 0.5 g QD administration. T>MIC was used as the pharmacokinetic/pharmacodynamic (PK/PD) index and calculated using MIC90 for Pseudomonas aeruginosa. Compared to the PK profile predicted at 2 g BID for patient with normal renal function, results suggest the following:
1. For patients with renal impairment managed without hemodialysis, CFPM 2 g BID for Ccr>50 mL/min, 0.5-1 g BID for Ccr 10-50 mL/min, and 0.5-1 g QD for Ccr<10mL/min show sufficient T>MIC90 that predict clinical effects without excessive accumulation.
2. For patients with renal impairment managed with hemodialysis modeled as three times a week, CFPM 1 g loading dose followed by 0.5 g QD dose just after hemodialysis avoids marked T>MIC90 decrease and reaches sufficient T>MIC90 while hemodialysis removes CFPM from blood and rapidly decreases serum concentrations.
3. No dose adjustment in BW from 40 to 90 kg is required for patients with renal impairment managed with or without hemodialysis since no remarkable changes in PK profiles and T>MIC90 were estimated within the BW range.
Key word
cefepime, population PK, renal impairment, dose
Received
February 7, 2005
Accepted
March 29, 2005
Jpn. J. Chemother. 53 (5): 302-308, 2005
