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 0.5-2g of CFPM once (QD) or twice (BID) a day in patients with Ccr from 5 to 50mL/min and BW between 40kg and 90kg. For late-stage renal failure patients undergoing hemodialysis, PK profiles of CFPM after a 1g loading dose followed by 0.5g QD dose were estimated in patients with Ccr of 5mL min by a PPK model modified with hemodialysis clearance. Hemodialysis was modeled as three times a week just before CFPM 0.5g 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 2g 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>50mL/min, 0.5-1g BID for Ccr 10-50mL min, and 0.5-1g QD for Ccr<10mL, minshow 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 1g loading dose followed by 0.5g 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 90kg is required for patients with renal impairment managed with or without hemodialysis since no remarkable changes in PK profiles and T>MIC. were estimated within the BW range.
