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*Clinical Research, Fresenius Kabi, Bad Homburg; M.A.R.C.O. Biostatistics Institute, Düsseldorf, Germany; and Medical Department, Fresenius Kabi France, formerly Anesthesia Department, Hôpital Pitié-Salpêtrière, Paris, France
Address correspondence and reprint requests to Cornelius Jungheinrich, MD, Clinical Research, Fresenius Kabi, 61346 Bad Homburg, Germany. Address e-mail to Cornelius.Jungheinrich@ fresenius-kabi.com.
Hydroxyethyl starches (HES) are almost exclusively excreted glomerularly, in part after hydrolysis by amylase. HES 130/0.4 (Voluven®; Fresenius Kabi Deutschland GmbH, Bad Homburg, Germany) was developed to improve pharmacokinetics whereas preserving the efficacy of volume effect. We studied the dependency of pharmacokinetics of HES 130/0.4 on renal function. Nineteen volunteers with stable, non-anuric renal dysfunction, ranging from almost normal creatinine clearance (CLcr) to severe renal impairment (mean CLcr: 50.6 mL · min-1 · 1.73 m-2), were given a single infusion of 500 mL 6% HES 130/0.4 over 30 min. HES plasma concentrations were determined until 72 h, urinary excretion until 72–96 h. CLcr had been obtained at least twice before and twice after dosing. Standard pharmacokinetic calculations and regression analysis were performed. Area under the time concentration curve (AUC0–inf) clearly depended on renal function comparing subjects with CLcr <50 with those with CLcr 
50 (ratio 1.73). Peak concentration (Cmax, 4.34 mg/mL) as well as terminal half-life (16.1 h, model independent) were not affected by renal impairment. At CLcr 30, 59% of the drug could be retrieved in urine, versus 51% at CLcr 15–<30. The mean molecular weight of HES in plasma was 62,704 d at 30 min, showing lower values with increased renal impairment (P = 0.04). Pre-dose amylase concentrations inversely correlated with baseline CLcr. Residual HES plasma concentrations after 24 h were small in all subjects (
0.6 mg/mL). We conclude that HES 130/0.4 (500 mL 6%) can be safely administered to patients even with severe renal impairment, as long as urine flow is preserved, without plasma accumulation.
IMPLICATIONS: Dependency of the pharmacokinetics of hydroxyethyl starch 130/0.4 on renal function was studied. The area under the time concentration curve increased moderately with more severe renal dysfunction; however, small plasma concentrations were observed after 24 h. Terminal half-life and peak concentration remained unaffected by renal impairment.
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