AIMS: 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 Blood samples (n = 407) for the determination of cefuroxime were withdrawn according to a sparse data sampling schedule and analysed by liquid chromatography mass spectrometry.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.
AIMS: 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 Blood samples (n = 407) for the determination of cefuroxime were withdrawn according to a sparse data sampling schedule and analysed by liquid chromatography mass spectrometry.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.
Authors: R W Bundtzen; R D Toothaker; O S Nielson; P O Madsen; P G Welling; W A Craig Journal: Antimicrob Agents Chemother Date: 1981-03 Impact factor: 5.191
Authors: J Broekhuysen; F Deger; J Douchamps; E Freschi; N Mal; P Neve; R Parfait; G Siska; M Winand Journal: Br J Clin Pharmacol Date: 1981-12 Impact factor: 4.335
Authors: A Hosmann; L C Ritscher; H Burgmann; Z Oesterreicher; W Jäger; S Poschner; E Knosp; A Reinprecht; A Gruber; M Zeitlinger Journal: Antimicrob Agents Chemother Date: 2018-01-25 Impact factor: 5.191
Authors: Saeed A Alqahtani; Abdullah S Alsultan; Hussain M Alqattan; Ahmed Eldemerdash; Turki B Albacker Journal: Antimicrob Agents Chemother Date: 2018-03-27 Impact factor: 5.191
Authors: Hanadi H Alrammaal; Khaled Abduljalil; Victoria Hodgetts Morton; R Katie Morris; John F Marriott; Hsu P Chong; Hannah K Batchelor Journal: Pharmaceutics Date: 2022-05-30 Impact factor: 6.525
Authors: Jennifer H Huang; Rachel Sunstrom; Myrna Y Munar; Ganesh Cherala; Arthur Legg; Ali J Olyeai; Stephen M Langley Journal: J Thorac Cardiovasc Surg Date: 2014-01-15 Impact factor: 5.209
Authors: Ralph Gertler; Michael Gruber; Gunther Wiesner; Stanislas Grassin-Delyle; Saïk Urien; Peter Tassani-Prell; Klaus Martin Journal: Br J Clin Pharmacol Date: 2018-06-15 Impact factor: 4.335
Authors: Pieter A J G De Cock; Joseph F Standing; Charlotte I S Barker; Annick de Jaeger; Evelyn Dhont; Mieke Carlier; Alain G Verstraete; Joris R Delanghe; Hugo Robays; Peter De Paepe Journal: Antimicrob Agents Chemother Date: 2015-09-08 Impact factor: 5.191