Evaluation of the clinical application of cystatin C, a new marker of the glomerular filtration rate, for the initial dose-setting of arbekacin

• Published in: Journal of clinical pharmacy and therapeutics Vol. 33; no. 3; pp. 227 - 235
• Main Authors: Otsuka, T., Tanaka, A., Suemaru, K., Inoue, T., Nishimiya, T., Murase, M., Araki, H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2008; Blackwell
• Subjects: Aged; Aged, 80 and over; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; arbekacin; Biological and medical sciences; Biomarkers - blood; creatinine; Creatinine - blood; Cystatin C; Cystatins - blood; Dibekacin - administration & dosage; Dibekacin - analogs & derivatives; Dibekacin - pharmacokinetics; Drug Monitoring; Female; Glomerular Filtration Rate; Hospitals, University; Humans; initial dose setting; Male; Medical sciences; Methicillin Resistance; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Pharmacology. Drug treatments; Renal failure; renal impairment; Renal Insufficiency - blood; Renal Insufficiency - diagnosis; Renal Insufficiency - metabolism; Staphylococcal Infections - drug therapy; Staphylococcal Infections - metabolism; Staphylococcus aureus; Kidney disease; Creatinine; Evaluation; Urinary system disease; Glomerular filtration; glomerular filtration rate; Biological marker; Arbekacin; Antibiotic; Nephropathy; Aminoglycoside; Renal failure; Cystatin C; initial dose setting; Protein synthesis inhibitor; Antibacterial agent; Dose; renal impairment
• ISSN: 0269-4727; 1365-2710
• DOI: 10.1111/j.1365-2710.2008.00905.x

Summary Objective:  Recent studies have shown that serum cystatin C is a better marker for measuring the glomerular filtration rate (GFR) than the conventional method, using serum creatinine concentration. The purpose of this study is to evaluate the clinical application of serum cystatin C as a marker of GFR to determine the initial dosage of arbekacin, an antibiotic primarily excreted via the kidneys. In this study, the predictability of serum arbekacin peak and trough concentrations were assessed using estimated population mean GFR values calculated from either serum creatinine (Cockcroft–Gault equation) or cystatin C (Sjöström equation) concentrations. Method:  Ninety‐five patients treated with arbekacin for methicillin‐resistant Staphylococcus aureus infection were divided into three groups according to their GFR values estimated by the serum cystatin C concentration as follows: normal to mild (GFR > 70 mL/min, n = 40), moderate (30 ≤ GFR ≤ 70 mL/min, n = 41) and severe (GFR < 30 mL/min, n = 14) renal impairment. Result:  The mean GFR (±SD) of 95 patients predicted by serum cystatin C concentration (64·6 ± 30·6 mL/min) was significantly lower (P < 0·001) than predicted by serum creatinine concentration (77·4 ± 43·9 mL/min). Prediction (difference of mean prediction error, ΔME) of the serum arbekacin concentration using the estimated GFR based on the serum cystatin C concentration was significantly less biased at the peak and trough concentrations than those determined using serum creatinine concentration. The accuracy of prediction (difference of the mean absolute error, ΔMAE) using serum cystatin C concentration was significantly better than with serum creatinine for both serum peak and trough concentrations in patients with moderately decreased GFR. However, there were no significant differences in the ΔMAE of normal to mild and severe renally impaired patients. Conclusion:  These results suggest that serum cystatin C is a useful marker of GFR for determining the initial dosage of arbekacin, especially in patients with moderate impairment of renal function.