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(R); 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, nonanuric 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 (AUC(0-inf)) clearly depended on renal function comparing subjects with CLcr <50 with those with CLcr greater than or equal to50 (ratio 1.73). Peak concentration (C-max, 4.34 mg/mL) as well as terminal half-life (16.1 h, model independent) were not affected by renal impairment. At CLcr greater than or equal to30,59'% 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). Predose amylase concentrations inversely correlated with baseline CLcr. Residual HES plasma concentrations after 24 h were small in all subjects (less than or equal to0.6 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.