[Interest of cystatin C for individual dosing of anticancer drugs cleared by the kidneys].
Cystatin C is a protein freely filtered in the renal glomerulus, then reabsorbed and completely metabolised within the tubular cells. The possibility to predict the clearance of compounds eliminated by the kidneys (and then to control their interindividual variability) was evaluated for two cytotoxic drugs (carboplatin and topotecan) in adults and EDTA (ethylene diamine tetraacetic acid), a compound used to determine the glomerular filtration rate in children. The population pharmacokinetic approach based on NONMEM program was used. For each of the three compounds, the cystatin C serum level was better predictive of clearance than that of creatinine. Moreover, for carboplatin and EDTA, the best equation between clearance and patients' characteristics included both cystatin C and creatinine level. A generalisation of cystatin C assay would contribute to standardise the clinical practices in Oncology.
Thomas
Fabienne
F
Institut Claudius-Regaud, EA3035 Pharmacologie Clinique et Expérimentale des Médicaments Anti-Cancéreux, et UFR de Pharmacie, Université Paul-Sabatier, 20-24 rue du Pont Saint Pierre, 31052 Toulouse, France.
Séronie-Vivien
Sophie
S
Malard
Laurence
L
Chatelut
Etienne
E
D000328:Adult; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002556:Cerebrospinal Fluid Proteins / Q000097:blood; D002648:Child; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D004492:Edetic Acid / Q000493:pharmacokinetics; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000378:metabolism; D008657:Metabolic Clearance Rate
D000970:Antineoplastic Agents; D015415:Biomarkers; C525030:CST3 protein, human; D002556:Cerebrospinal Fluid Proteins; D055316:Cystatin C; D015891:Cystatins; D004492:Edetic Acid