Cystatin C for therapeutic drug monitoring.

A 78-year-old man with prostate cancer needed intravenous treatment with amikacin for a suspected gramnegative bacillary respiratory infection. He had a body surface area of 1.97 m, weight of 78 kg, and body mass index of 29 kg/m. Laboratory test results are shown in Table 1. Because the initial renal function was judged to be normal and the patient was considered overweight, the antibiotic was empirically administered at 12 mg/kg once daily (1000 mg/24 h). Predose and peak concentrations (obtained 0.5 h after completion of the intravenous dose of amikacin) were measured by a homogeneous immunoassay (Cobas Integra®, Roche) to confirm that the dosage was correct. Concentrations were fitted to a 1-compartment model using Bayesian analysis (PKS®, Abbott). Because the new estimated glomerular filtration (GFR) rate equations, such as Modification of Diet in Renal Disease– isotope dilution mass spectrometry (MDRD-IDMS) or CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), are not included in the software, estimations for dose adjustment were carried out using the creatinine clearance (CrCl) calculated by the Cockcroft-Gault (CG) formula. Serum creatinine (sCr) was measured by the compensated Jaffe kinetic method (IDMS-traceable assay). Adjustment of aminoglycoside dosage sought to maintain concentrations within the therapeutic intervals. Fig. 1 shows amikacin concentrations determined in our patient as well as the dosage regimens. On the fifth day from the beginning of the antibiotic treatment, the amikacin volume of distribution and clearance estimated by applying the population pharmacokinetic equations and taking into account the CrCl were 0.25 (0.07) L/kg and 0.04 (0.01) mL min 1 kg , respectively. The predose concentration predicted from these parameters was 0.3 g/mL, which was lower than the observed concentration in our patient (10.6 g/mL). The presence of drug interactions with comedications was ruled out by using the Lexi-InteractTM online database. However, the patient also suffered from liver injury (Table 1). Because it has been proven that in advanced liver diseases or liver cirrhosis an overestimation of the GFR occurs when sCr is used, the measurement of serum cystatin C (CysC) was recommended to detect a possibly impaired renal function. Pending this measurement, a new dosing scheme of 750 mg/36 h was recommended.