A population pharmacokinetic model for cefuroxime using cystatin C as a marker of renal function.
OBJECTIVE
Since cefuroxime mainly is excreted by renal filtration, dosing is currently based on serum creatinine (Scr) or creatinine clearance (CLcr). However, it has been suggested that cystatin C (CysC) is superior to Scr as a marker of renal function. The aim of this prospective study was to develop a population model that describes the pharmacokinetics of cefuroxime and to investigate the usefulness of CysC as a covariate of the model parameters.


METHODS
Ninety-seven patients were studied (CLcr range 6.5-115 ml min(-1)). Blood samples (n = 407) for the determination of cefuroxime were withdrawn according to a sparse data sampling schedule and analysed by liquid chromatography mass spectrometry. The population analysis was performed in NONMEM.


RESULTS
A two-compartment model described the data well. The biomarkers Scr, CLcr and CysC were evaluated as covariates on clearance (CL). The model that included CysC generated the best fit. In the final population model CL was a function of CysC and body weight, whereas V(1) was only a function of body weight. Final parameter estimates (relative standard errors) were 6.00 (3.2%) l h(-1), 11.4 (5.3%) l and 5.11 (11%) l for CL, V(1) and V(2), respectively.


CONCLUSIONS
Based on the results of the present study, and because CysC is practical to use in the clinic, it is suggested that individual dosing of cefuroxime may be based on CysC rather than on Scr or CLcr. Furthermore, our final population model may be useful as a tool when designing new dosing schedules for cefuroxime.
Viberg
Anders
A
Division of Pharmokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. anders.viberg@farmbio.uu.se
Lannergård
Anders
A
Larsson
Anders
A
Cars
Otto
O
Karlsson
Mats O
MO
Sandström
Marie
M
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000378:metabolism; D002444:Cefuroxime / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055316:Cystatin C; D015891:Cystatins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged
D000900:Anti-Bacterial Agents; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D002444:Cefuroxime