Tissue storage of 14C-labelled hydroxyethyl starch (HES) 130/0.4 and HES 200/0.5 after repeated intravenous administration to rats

被引:45
作者
Jost Leuschner
Jens Opitz
Andreas Winkler
Roland Scharpf
Frank Bepperling
机构
[1] LPT Lab. of Pharmacology/Toxicology, Hamburg
[2] Fresenius Kabi Deutschland GmbH, Clinical Research
关键词
Hydroxyethyl Starch; Tissue Storage; Peripheral Arterial Occlusive Disease; Sudden Hearing Loss; Hydroxyethyl Group;
D O I
10.2165/00126839-200304060-00001
中图分类号
学科分类号
摘要
Objective: To investigate the effect of the molar substitution of hydroxyethyl starch (HES) solutions on tissue and organ storage in rats after repeated administration. Study design: A controlled, multiple-dose study was performed in 48 rats. Daily bolus injections of 0.7 g/kg of 10% HES 130/0.4 or 10% HES 200/0.5 were administered on 18 consecutive days. In order to examine quantitatively the distribution and excretion of both preparations on HES tissue storage, radiolabelled HES was measured 3, 10, 24 and 52 days after the last administration. Tissue storage was expressed as percentage radioactivity of total administered HES dose in the total body, carcass, liver, kidney, spleen, lymph nodes, plasma and urine. Results: 52 days after the last administration the remaining radioactivity of labelled HES 200/0.5 was nearly 4-fold higher compared with HES 130/0.4 in the total body (2.45% vs 0.65% of the total administered dose). This difference in tissue storage was statistically significant (p ≤ 0.01). A comparable difference was observed for the liver and carcass. Conclusion: Tissue storage after repeated administration of an HES solution with a low molar substitution (0.4) was significantly lower in the total body as well as in the liver and carcass compared with an HES solution with a medium molar substitution (0.5). However, the potential clinical consequences of these present findings have not yet been determined.
引用
收藏
页码:331 / 338
页数:7
相关论文
共 28 条
  • [1] Treib J., Baron J.F., Grauer M.T., Et al., An international view of hydroxyethyl starches, Intensive Care Med., 25, pp. 258-268, (1999)
  • [2] Treib J., Haass A., Pindur G., Et al., Influence of the C2/C6 hydroxyethylation ratio of hydroxyethyl starch (HES) on hemorheology, coagulation and elimination kinetics, Thromb. Haemost., 78, pp. 1452-1456, (1995)
  • [3] Mishler J.M., Pharmacology of Hydroxyethyl Starch, (1982)
  • [4] Stander S., Szepfalusi Z., Bohle B., Et al., Differential storage of hydroxyethyl starch (HES) in the skin: An immunoelectron-microscopical long-term study, Cell Tissue Res., 304, pp. 261-269, (2001)
  • [5] Reimann S., Szepfalusi Z., Kraft D., Et al., Hydroxyethylstärke-Speicherung in der Haut unter besonderer Berücksichtigung des Hydroxyethylstärke-assozierten Juckreizes, Dtsch. Med. Wochenschr., 125, pp. 280-285, (2000)
  • [6] Gall H., Kaufmann R., von Ehr M., Et al., Persistierender Pruritus nach Hydroxyäthylstärke-Infusionen, Hautarzt, 44, pp. 713-716, (1993)
  • [7] Kiesewetter H., Blume J., Jung F., Et al., Haemodilution with medium molecular weight hydroxyethyl starch in patients with peripheral arterial occlusive disease stage IIb, J. Intern. Med., 227, pp. 107-114, (1990)
  • [8] Hulse J.D., Yacobi A., Hetastarch: An overview of the colloid and its metabolism, Drug Intell. Clin. Pharm., 17, pp. 334-341, (1983)
  • [9] Waitzinger J., Bepperling F., Papst G., Et al., Pharmacokinetics and tolerability of a new hydroxyethyl starch (HES) specification (HES 130/0.4) after single-dose infusion of 6% or 10% solutions in healthy volunteers, Clin. Drug Invest., 16, pp. 151-160, (1998)
  • [10] Jungheinrich C., Scharpf R., Wargenau M., Et al., The pharmacokinetics and tolerability of an intravenous infusion of the new hydroxyethyl starch 130/0.4 (6%, 500ml) in mild-to-severe renal impairment, Anesth. Analg., 95, pp. 544-551, (2002)