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Pharmacokinetics of Ferric bepectate - a new intravenous iron drug for treating iron deficiency

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@article{1d4c1cfffb88430ba0b9cf8c03d9d3f6,
title = "Pharmacokinetics of Ferric bepectate - a new intravenous iron drug for treating iron deficiency",
abstract = "IV iron is indicated in clinical conditions, where rapid anaemia alleviation and repletion of iron stores are required. The acute toxicity of IV iron is ascribed to the presence of labile iron in plasma. Thus, shorter plasma residence time might improve the safety profile, even for compounds holding-on the iron tightly. In this single-centre, open-label, single-dose escalation study, we evaluated the elimination kinetics of ferric bepectate (FBP) compared to those of ferric carboxymaltose (FCM). Thirty-three iron-depleted anaemic patients who had undergone cardiac surgery were included and received 200, 500 or 1500 mg FBP or 500 mg FCM. Plasma drug curves were subjected to model-free analysis. Because saturation kinetics was found, a compartmental model with limited elimination capacity was applied. Urinary iron excretion was also analysed. The initial non-compartmental analysis revealed an increasing AUC/dose ratio for FBP. For both drugs, the central distribution compartment corresponded to plasma volume, and elimination followed Michaelis-Menten saturation kinetics. Maximal elimination rates (Vmax) were 224 mg/hr and 81 mg/hr for FBP 500 mg and FCM 500 mg, respectively; drug concentrations at half Vmax (Km), 99 mg/L and 212 mg/L, respectively; and terminal plasma half-life (T½), 3.05 hr and 8.96 hr, respectively. Both drugs were equally effective in eliciting an early ferritin rise. Urinary iron excretion was measurable in all patients receiving FCM but not in those receiving FBP, which was well tolerated. Intravenous iron drugs are subject to capacity-limited elimination with different saturation thresholds. Urinary iron excretion can be used as a surrogate for labile plasma iron. This article is protected by copyright. All rights reserved.",
keywords = "intravenous iron drugs, labile iron, michaelis-menten kinetics, side effects, urinary iron, Prospective Studies, Anemia, Iron-Deficiency/blood, Ferric Compounds/administration & dosage, Humans, Middle Aged, Male, Maltose/administration & dosage, Renal Elimination, Dose-Response Relationship, Drug, Iron/blood, Aged, Infusions, Intravenous",
author = "Manuel Mu{\~n}oz and Olsen, {Peter Skov} and Petersen, {Tonny Studsgaard} and Susanne Manhart and Stig Waldorff",
note = "{\textcopyright} 2019 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).",
year = "2019",
month = aug,
doi = "10.1111/bcpt.13219",
language = "English",
volume = "125",
pages = "133--141",
journal = "Basic & Clinical Pharmacology & Toxicology Online",
issn = "1742-7843",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "2",

}

RIS

TY - JOUR

T1 - Pharmacokinetics of Ferric bepectate - a new intravenous iron drug for treating iron deficiency

AU - Muñoz, Manuel

AU - Olsen, Peter Skov

AU - Petersen, Tonny Studsgaard

AU - Manhart, Susanne

AU - Waldorff, Stig

N1 - © 2019 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

PY - 2019/8

Y1 - 2019/8

N2 - IV iron is indicated in clinical conditions, where rapid anaemia alleviation and repletion of iron stores are required. The acute toxicity of IV iron is ascribed to the presence of labile iron in plasma. Thus, shorter plasma residence time might improve the safety profile, even for compounds holding-on the iron tightly. In this single-centre, open-label, single-dose escalation study, we evaluated the elimination kinetics of ferric bepectate (FBP) compared to those of ferric carboxymaltose (FCM). Thirty-three iron-depleted anaemic patients who had undergone cardiac surgery were included and received 200, 500 or 1500 mg FBP or 500 mg FCM. Plasma drug curves were subjected to model-free analysis. Because saturation kinetics was found, a compartmental model with limited elimination capacity was applied. Urinary iron excretion was also analysed. The initial non-compartmental analysis revealed an increasing AUC/dose ratio for FBP. For both drugs, the central distribution compartment corresponded to plasma volume, and elimination followed Michaelis-Menten saturation kinetics. Maximal elimination rates (Vmax) were 224 mg/hr and 81 mg/hr for FBP 500 mg and FCM 500 mg, respectively; drug concentrations at half Vmax (Km), 99 mg/L and 212 mg/L, respectively; and terminal plasma half-life (T½), 3.05 hr and 8.96 hr, respectively. Both drugs were equally effective in eliciting an early ferritin rise. Urinary iron excretion was measurable in all patients receiving FCM but not in those receiving FBP, which was well tolerated. Intravenous iron drugs are subject to capacity-limited elimination with different saturation thresholds. Urinary iron excretion can be used as a surrogate for labile plasma iron. This article is protected by copyright. All rights reserved.

AB - IV iron is indicated in clinical conditions, where rapid anaemia alleviation and repletion of iron stores are required. The acute toxicity of IV iron is ascribed to the presence of labile iron in plasma. Thus, shorter plasma residence time might improve the safety profile, even for compounds holding-on the iron tightly. In this single-centre, open-label, single-dose escalation study, we evaluated the elimination kinetics of ferric bepectate (FBP) compared to those of ferric carboxymaltose (FCM). Thirty-three iron-depleted anaemic patients who had undergone cardiac surgery were included and received 200, 500 or 1500 mg FBP or 500 mg FCM. Plasma drug curves were subjected to model-free analysis. Because saturation kinetics was found, a compartmental model with limited elimination capacity was applied. Urinary iron excretion was also analysed. The initial non-compartmental analysis revealed an increasing AUC/dose ratio for FBP. For both drugs, the central distribution compartment corresponded to plasma volume, and elimination followed Michaelis-Menten saturation kinetics. Maximal elimination rates (Vmax) were 224 mg/hr and 81 mg/hr for FBP 500 mg and FCM 500 mg, respectively; drug concentrations at half Vmax (Km), 99 mg/L and 212 mg/L, respectively; and terminal plasma half-life (T½), 3.05 hr and 8.96 hr, respectively. Both drugs were equally effective in eliciting an early ferritin rise. Urinary iron excretion was measurable in all patients receiving FCM but not in those receiving FBP, which was well tolerated. Intravenous iron drugs are subject to capacity-limited elimination with different saturation thresholds. Urinary iron excretion can be used as a surrogate for labile plasma iron. This article is protected by copyright. All rights reserved.

KW - intravenous iron drugs

KW - labile iron

KW - michaelis-menten kinetics

KW - side effects

KW - urinary iron

KW - Prospective Studies

KW - Anemia, Iron-Deficiency/blood

KW - Ferric Compounds/administration & dosage

KW - Humans

KW - Middle Aged

KW - Male

KW - Maltose/administration & dosage

KW - Renal Elimination

KW - Dose-Response Relationship, Drug

KW - Iron/blood

KW - Aged

KW - Infusions, Intravenous

U2 - 10.1111/bcpt.13219

DO - 10.1111/bcpt.13219

M3 - Journal article

C2 - 30839153

VL - 125

SP - 133

EP - 141

JO - Basic & Clinical Pharmacology & Toxicology Online

JF - Basic & Clinical Pharmacology & Toxicology Online

SN - 1742-7843

IS - 2

ER -

ID: 56798991