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.
ABSTRACT 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 (CL(cr)) to severe renal impairment (mean CL(cr): 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. CL(cr) 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 CL(cr) < 50 with those with CL(cr) > or =50 (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 CL(cr) > or =30, 59% of the drug could be retrieved in urine, versus 51% at CL(cr) 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 CL(cr). Residual HES plasma concentrations after 24 h were small in all subjects (< or =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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Article: 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.
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ABSTRACT: Proper fluid management is crucial for the management of critically ill patients. However, there is a continuing debate about the choice of the fluid, i.e., crystalloid vs. colloid. Colloid solution is theoretically advantageous to the crystalloid because of larger volume effect and less interstitial fluid accumulation, and hydroxyethyl starch (HES) is most frequently used for perioperative setting. Nevertheless, application of HES solution is relatively limited due to its side effects including renal toxicity and coagulopathy. Since prolonged presence of large HES molecule is responsible for these side effects, rapidly degradable HES solution with low degree of substitution (tetrastarch) supposedly has less potential for negative effects. Thus, tetrastarch may be more frequently used in the ICU setting. However, several large-scale randomized trials reported that administration of tetrastarch solution to the patients with severe sepsis has negative effects on mortality and renal function. These results triggered further debate and regulatory responses around the world. This narrative review intended to describe the currently available evidence about the advantages and disadvantages of tetrastarch in the ICU setting.03/2014; 2(1):23. DOI:10.1186/2052-0492-2-23
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ABSTRACT: Orally administered drugs usually face the problem of low water solubility, low permeability and less retention in blood stream leading to unsatisfactory pharmacokinetic profile of drugs. Polymer conjugation has attracted increasing interest in pharmaceutical industry for delivering such low molecular weight (Mw) drugs as well as some complex compounds. In the present work, degraded and oxidized hydroxyethyl starch (HES), a highly biocompatible semi-synthetic biopolymer, was used as a drug carrier to overcome the solubility and permeability problems. The HES was coupled with synthesized N-arylsulfonylbenzimidazolones, a class of sulfonylurea derivatives, by creating an amide linkage between the two units. The coupled products were characterized using GPC, IR, 1H NMR and 13C NMR spectroscopy. The experiments established the viability of a covalent coupling between the biopolymer and N-arylsulfonylbenzimidazoles. The coupled products were screened for their in vivo antidiabetic potential on male albino rats. The coupling of sulfonylurea derivatives with HES resulted in a marked increase of the hypoglycemic activity of all the compounds. 2,3-Dihydro-3-(4-nitrobenzensulfonyl)-2-oxo-1H-benzimidazole coupled to HES10100, was found most potent with a 67 % reduction in blood glucose level of the rats as compared to 41 % reduction produced by tolbutamide and 38 % by metformin.Bioconjugate Chemistry 12/2014; 26(1). DOI:10.1021/bc500509a · 4.82 Impact Factor
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ABSTRACT: Hydroxyethyl starch (HES) family has been one of the cornerstones in fluid management for over four decades. Recent evidence from clinical studies and meta-analyses has raised few concerns about the safety of these fluids, especially in certain subpopulations of patients. High-quality clinical trials and meta-analyses have emphasized nephrotoxic effects, increased risk of bleeding, and a trend toward higher mortality in these patients after the use of HES solutions. Scientific evidence was derived from international guidelines, aggregated research literature, and opinion-based evidence was obtained from surveys and other activities (e.g., internet postings). On critical analysis of the current data available, it can be summarized that further large scale trials are still indicated before HES can be discarded.Journal of Anaesthesiology Clinical Pharmacology 01/2014; 30(4):472-480. DOI:10.4103/0970-9185.142801