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EFFECTS OF INTRAVENOUS ABT‐870 (IRON (III)‐HYDROXIDE OLIGOSACCHARIDE) ON MEAN ARTERIAL PRESSURE AND HEART RATE IN THE ANAESTHETIZED BEAGLE: COMPARISON WITH OTHER IRON‐CONTAINING HAEMATINIC AGENTS
Author(s) -
Preusser Lee C,
Fryer Ryan M,
Gerhardt Armin,
Hu Yanhui,
DelgadoHerrera Leticia,
Melnick Joel Z,
Williams Laura A,
Cox Bryan F,
Reinhart Glenn A
Publication year - 2005
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2005.tb00001.x
Subject(s) - iron sucrose , chemistry , blood pressure , heart rate , mean arterial pressure , beagle , medicine , pharmacology , anesthesia , anemia , iron deficiency , intravenous iron
SUMMARY Iron‐deficiency anaemia, a complication of end‐stage renal disease (ESRD), is often treated with parenteral iron therapies that have been shown to produce dose‐limiting hypotension in patients. ABT‐870 (iron‐(III)hydroxide‐oligosaccharide) is comprised of elemental iron complexed with oligosaccharide, a composition that we hypothesised would allow the hypotensive effects of parenteral iron therapy to be overcome, thus allowing a rapid rate of infusion to be well tolerated. Mean arterial pressure (MAP) and heart rate (HR) were monitored in anaesthetized dogs following the infusion of ABT‐870 and iron sucrose administered at doses of 7.1 and 21.3 mg/kg using a rapid 30 s infusion. ABT‐870 and iron sucrose were also monitored at doses of 7.1, 21.3 and 50 mg/kg administered over a 10 min period. Sodium ferric gluconate complex (SFGC) was administered in an identical fashion at doses of 12.5 and 31.2 mg/kg. A 30 s rapid infusion of ABT‐870 at doses of 7.1 and 14.3 mg/kg or a 10 min infusion of ABT‐870 at doses of 7.1 and 21.3 mg/kg produced little effect on MAP and HR. Infusion of the highest dose of ABT‐870 (50 mg/kg) produced no consistent hypotension, but did produce an increase in HR (maximal increase 35 ± 9 b.p.m.), an effect that lasted only 15 min. A 30 s rapid infusion of iron sucrose at 7.1 mg/kg produced modest increases in MAP and HR (5 ± 1 mmHg and 5 ± 2 b.p.m., respectively). However, rapid infusion of iron sucrose at 14.3 mg/kg produced hypotension (to ‐8 ± 1 mmHg below baseline) and exerted variable, biphasic effects on HR ranging from ‐16 to +50 b.p.m. Although 10 min infusion of iron sucrose at 7.1 mg/kg exerted little effect on MAP and HR, at doses of 21.3 and 50 mg/kg iron sucrose elicited a profound dose‐dependent decrease in MAP (‐34 ± 11 and ‐83 ± 5 mmHg, respectively) and a pronounced increase in HR ranging from 32 to 49 b.p.m. above baseline. A 10 min infusion of SFGC at doses of 12.5 and 31.2 mg/kg produced a dose‐dependent decrease in MAP (‐28 ± 18 and ‐67 ± 12 mmHg below baseline) and a marked increase in HR (26 ± 11 and 94 ± 15 b.p.m. above baseline). In conclusion, unlike iron sucrose and SFGC, high doses of ABT‐870 failed to exert consistent hypotensive effects. These data demonstrate that ABT‐870 may have a substantial therapeutic window and considerable clinical potential for iron‐replacement therapy.