Adsorption of Human Recombinant Erythropoietin on Dialysis Membranes In Vitro

Mori, Hideki; Hiraoka, Kazuyuki; Yorifuji, Ryoichi; Iwasaki, Tomoko; Gomikawa, Syuzo; Inagaki, Oshi; Inoue, Seishi; Takamitsu, Yoshihiro; Fujita, Yoshikazu

doi:10.1111/j.1525-1594.1994.tb03309.x

Cited by 11 publications

(9 citation statements)

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“…It is well‐accepted that the haemodialyser membrane can adsorb some solutes, especially proteins. It is also reported that several drugs, such as erythropoietin, adsorb to dialyser membrane [14]. Previous studies on the adsorption of the drug were generally done in vitro without serum or protein.…”

Section: Discussionmentioning

confidence: 99%

Adsorption of oxacalcitriol by polysulphone haemodialyser in patients with secondary hyperparathyroidism

Tsuruoka

Yamamoto

Ioka

et al. 2004

Brit J Clinical Pharma

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Br J Clin PharmacolBritish Journal of Clinical Pharmacology DOI:10.1111DOI:10. /j.1365DOI:10. -2125DOI:10. .2004 AimsThis study was undertaken to evaluate removal of 22-oxacalcitriol (OCT), an active and intravenously used vitamin D3 analogue with less calcaemic activity, by polysulphone haemodialyser in vivo and in vitro . We further compared the pharmacodynamic efficacy [suppression of intact parathyroid hormone (iPTH)] when g iven intravenously either during or at the end of the haemodialysis. Methods(i) Drug clearance by the polysulphone dialyser was measured during a single continuous infusion (5 m g) for 30 min into the arterial side of the dialyser in endstage renal failure patients with secondary hyperparathyroidism ( n = 7). (ii) The drug adsorption by the hollowfibre membrane during incubation for 30 min was measured in vitro . (iii) To evaluate efficacy, the drug was given (i.v. bolus) during or at the end of haemodialysis for 4 weeks in a cross-over fashion with a washout period of 8 weeks ( n = 9). Serum Ca 2 + , phosphate (P) and iPTH concentrations just before the initiation of the dialysis were monitored every week. Results(i) OCT was significantly cleared by the polysulphone haemodialyser, but the clearance declined in a time-dependent manner to approach zero at 30 min. Arterial (at the place between the drug infusion site and the haemodialyser column) drug concentrations did not change during the infusion (mean = 2064 ± 233 pg ml -1 ). Venous (just after the dialyser) drug concentrations at 10 min after the infusion were significantly lower than those of the arterial side (mean = 784 ± 84 pg ml -1 ); however, they increased with time and reached those of the arterial side at 30 min. (ii) In vitro , OCT was adsorbed by the membrane. The amount of adsorption was concentration-dependent and was lower in the presence of human serum (55 ± 4% without and 23 ± 4% with serum at 600 pg ml -1 of OCT). (iii) Although serum Ca 2 + and P increased and iPTH decreased by both treatment regimens (i.e. OCT administered either during or at the end of haemodialysis), these changes did not significantly differ. Mean differences (and 95% confidence interval) of Ca 2 + , P, and iPTH at the end of the trial were 0.03 ( -0.04, 0.09) m M , 0.41 ( -0.43, 1.26) mg dl -1 and 38 ( -42, 88) pg ml -1 , respectively. ConclusionOCT is adsorbed by polysulphone dialyser in vitro and in vivo . However, the pharmacodynamic effectiveness was largely independent of the administration reg imen of OCT given either during or at the end of haemodialysis. Adsorption of oxacalcitriol by haemodialyserBr J Clin Pharmacol 58 :5 489

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Section: Discussionmentioning

confidence: 99%

Adsorption of oxacalcitriol by polysulphone haemodialyser in patients with secondary hyperparathyroidism

Tsuruoka

Yamamoto

Ioka

et al. 2004

Brit J Clinical Pharma

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“…Epo may be adsorbed on polyamide filters the same way it binds to polyacrylonitrile membranes [14]. In the study performed by Ohls et al [15], a cellulose acetate filter was used to administer epoietin alpha (200 IU/kg/ day in a 4-hour PN solution infusion) instead of a synthetic polymer filter.…”

Section: Discussionmentioning

confidence: 99%

Stability and Biological Activity of Epoietin Beta in Parenteral Nutrition Solutions

Huynh-Delerme

Penaud²,

Lacombe³

et al. 2002

Neonatology

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The aim of this in vitro study was to determine stability and biological activity of epoietin (Epo) beta in a parenteral nutrition solution over 24 h. Epo beta was added to the parenteral nutrition solution which was administered through intravenous tubing and a Posidyne Neo filter. Samples were collected after 0, 4, 12, and 24 h. The Epo concentrations were measured before and after filter passage by an ELISA assay. The Epo biological activity was determined in the UT7/Epo cell line. The Epo concentration in the parenteral nutrition solution remained stable for 24 h. However, 35% of the Epo was adsorbed by the filter. The samples collected induced proliferation of UT7/Epo cells. These results suggest that Epo can be administered in parenteral nutrition solutions, but the dosage would need to be increased when a filter is used.

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“…1 Similar results were presented by Mori and colleagues, who found a signifi cant adsorption by polymethyl metacrylate and polyacrylonitrile membranes, but not by cuprophan, ethylene vinyl alcohol, or polysulfone membranes. 2 These studies were performed in the early 1990s. More recently, in a study performed on 211 patients undergoing dialysis using epoetin beta to correct anemia, Richardson and colleagues could not identify a signifi cant difference in need for epoetin through the use of a polysulfone/high-fl ux membrane over a modifi ed cellulose triacetate/midfl ux membrane, provided the patients were adequately dialyzed.…”

Section: Discussionmentioning

confidence: 99%

“…Several in vitro studies 1,2 have shown recombinant human erythropoietin (rhEPO) could be partly eliminated by membrane adsorption with some dialysis membranes (Mb). A more recent study suggested this might be the case only with high-fl ux membranes.…”

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Timing of the administration of intravenous darbepoetin alfa during the dialysis session: Does it impact efficacy?

Rottembourg¹,

Kpade²,

Dansaert³

et al. 2009

Dialysis & Transplantation

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BACKGROUND: Darbepoetin alfa (DA) is an erythropoietin-stimulating agent (ESA) preferably administered through intravenous (IV) route in hemodialysis (HD) patients. Although some in vitro studies suggest the possibility of partial adsorption of ESAs in dialysis membranes (Mb) and lines, these data are not clinically confi rmed.METHODS: This 12-month, prospective, single-center cross-over study assessed the impact of the time of IV DA injection during HD on hemoglobin (Hgb) level and ESA dosing. A total of 90 HD patients received IV DA once every other week (Q2W), delivered at 2 possible time points: the middle or end of the HD session. After 6 months, the injection time point was crossed over to the other timing modality for another 6 months.RESULTS: Demographics for both groups of patients were similar. Mean Hgb level remained stable from baseline to month 6 (not signifi cant) for both timing modality groups. The same was observed for DA dose. Hemodialysis session parameters, nutritional status, and Kt/V were similar and stable during the study. Mean transferrin saturation was 44% and serum ferritin was Ն100 g/L in more than 92% of patients. Iron supplementation remained unchanged and there were no blood transfusions during the study.CONCLUSIONS: Q2W DA maintained target Hgb concentrations. The lack of difference in Hgb levels and DA dosing between the 2 injection timings suggests a lack of clinically signifi cant adsorption/interaction between DA and dialysis Mb/lines. Therefore, timing of IV DA administration can be fl exible and adapted to the routine practice of each local dialysis unit.

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Adsorption of Human Recombinant Erythropoietin on Dialysis Membranes In Vitro

Cited by 11 publications

References 9 publications

Adsorption of oxacalcitriol by polysulphone haemodialyser in patients with secondary hyperparathyroidism

Adsorption of oxacalcitriol by polysulphone haemodialyser in patients with secondary hyperparathyroidism

Stability and Biological Activity of Epoietin Beta in Parenteral Nutrition Solutions

Timing of the administration of intravenous darbepoetin alfa during the dialysis session: Does it impact efficacy?

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