The Pharmacokinetics and Tolerability of an Intravenous Infusion of the New Hydroxyethyl Starch 130/0.4 (6%, 500 mL) in Mild-to-Severe Renal Impairment

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.