ISSN:0036-553X    

DOI:10.1111/j.1600-0609.1977.tb01209.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

ISSN:0036-553X    

DOI:10.1111/j.1600-0609.1977.tb01210.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

A preparation containing an iron‐poly (sorbitol‐gluconic acid) complex for parenteral treatment of iron deficiency anaemia is described. The physical and chemical properties of the iron complex have been studied by using electrophoresis and gel permeation chromatography. A rapid absorption from the injection site after intramuscular administration to rabbits takes place, 70 per cent of the iron being absorbed after 24—48 hours. Thereafter, the absorption rate is slower, and 32 days after the injection 94 per cent has been absorbed from the injection site. In rabbits the maximum level of iron in serum is reached after 12—24 hours; in dogs after 1—3 hours. Disappearance from the serum takes place slowly. The complex is exclusively absorbed via the lymphatic route. Nine to ten per cent of the given dose is excreted by the kidney within 72 hours in rats and 24 hours in rabbits after intramuscular administration. On administration of the preparation to rats, made anaemic by phlebotomy, a rapid increase of haemoglobin values is observed as well as a very high utilization of the retained amount of the g

ISSN:0036-553X    

DOI:10.1111/j.1600-0609.1977.tb01211.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

ISSN:0036-553X    

DOI:10.1111/j.1600-0609.1977.tb01212.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Intravenous injection of the iron‐poly (sorbitol‐gluconic acid) complex (IPSG) to cats anaesthetized with sodium pentobarbitone caused a transient decrease in mean arterial blood pressure and a temporary increase in central venous pressure, heart rate and femoral blood flow at large doses (cumulative doses up to 744 mg/kg). Tachyphylaxis developed upon repeated administration. A temporary reduction in the magnitude of the blood pressure responses to noradrenaline and isoprenaline was obtained after large doses of IPSG. The blood pressure effects of acetylcholine, histamine and bilateral carotid occlusion were not affected. No definite effects were seen on the electrocardiograms. The transient cardiovascular effects were interpreted as being due to the presence of small amounts of ferrous iron in the preparation.IPSG did not significantly affect blood coagulation or platelet aggregation as judged from results of in vitro and in vivo experiments.Immunogenicity studies in rabbits and antibody analyses of sera from patients treated with IPSG failed to demonstrate any effect of IPSG on the immune sys

ISSN:0036-553X    

DOI:10.1111/j.1600-0609.1977.tb01213.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

ISSN:0036-553X    

DOI:10.1111/j.1600-0609.1977.tb01214.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

The possible influence of Ferastral®, an iron‐poly (sorbitol‐gluconic acid) complex, on blood coagulation in man was investigated.Ferastral added to plasma produced no changes in blood coagulation until a final concentration of 2 000 μg/ml (35.8 mmol/l) was used, when minimal changes in blood coagulation factors were observed. Five patients were given an intramuscular injection of 250 mg Ferastral. No changes in blood coagulation and thrombocyte function were observed up to 5 hours after the initial iron inje

ISSN:0036-553X    

DOI:10.1111/j.1600-0609.1977.tb01215.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

ISSN:0036-553X    

DOI:10.1111/j.1600-0609.1977.tb01216.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

This paper presents a review of the toxicological studies in animals on Ferastral®, an iron‐poly (sorbitol‐gluconic acid) complex. Studies after single administration were performed in mice, rats and dogs, and LD50‐values were calculated in mice and rats. Studies after repeated administration were performed in rats and dogs. The test compound was given intramuscularly twice a week for five weeks to rats in doses varying from 50 to 400 mg Fe3+/kg, and to dogs from 5 to 200 mg Fe3+/kg. In a special study Ferastral was given intravenously to dogs every day for 12 days at the dose levels 5 and 20 mg Fe3+/kg. Imferon®, iron‐dextran, was used as a reference compound in some of the studies.Ferastral induced very little inflammatory reaction at the injection site. Depositions of iron‐containing pigments were found in all examined organs, being most pronounced at the intramuscular injection site, in the liver, spleen, and lymph nodes. Hyperplasia and hypertrophy as a reaction to the iron‐containing pigments resulted in increased weights of the liver and the spleen. Iron deposits in the liver occurred in both hepatocytes and Kupffer cells. With low doses the distribution was diffuse and with higher doses also focally accentuated. In both rats and dogs the focally accentuated distribution of iron in the liver was accompanied by granulomatous changes. There was a dose difference between rats and dogs. In rats iron was stored at the intramuscular injection site to a much greater extent than in dogs, and severe proliferation of iron‐loaded macrophages at the intramuscular injection site was seen in rats at much lower dose levels than in dogs. Imferon caused liver changes of similar appearance as those

ISSN:0036-553X    

DOI:10.1111/j.1600-0609.1977.tb01217.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

This paper presents a review of the teratological and peri‐ and postnatal studies performed in rats and rabbits on Ferastral®, an iron‐poly (sorbitol‐gluconic acid) complex. The test compound was given intramuscularly in doses varying from 1 to 100 mg Fe3+/kg. In the teratological studies the compound was given daily during the whole or part of the period of organogenesis, and in the peri‐ and postnatal study in rats from day 16 of pregnancy through lactation to 21 days post partum. In a separate study the effects of Ferastral® on blood coagulation and fibrinolysis were studied in pregnant rats treated with 50 mg Fe3+/kg. Jectofer® (iron‐sorbitol) and Imferon® (iron‐dextran) were used as reference compounds in some of the studies.Pregnant rats reacted in a totally different way compared to pregnant rabbits when treated with high doses of Ferastral. Pregnant rats, but not rabbits, developed focal necrosis in the liver, placenta and spleen. These changes were dose‐dependent and not observed with lower doses (1, 4 and 16 mg Fe3+/kg). Similar pathological alterations were also seen after treatment with Jectofer, but not with Imferon. The pathological changes, being similar to those seen after elicitation of a generalized Shwartzman reaction (GSR), were not interpreted as an expression of such a reaction. The most common features of the GSR, bilateral cortical necrosis, capillary thrombi, and changes in the blood coagulation and fibrinolytic activity, were not observed in the pregnant rats.The maternal toxicity was accompanied by secondary effects on the foetuses manifested in reduced maturation of the foetal skeleton. Treatment with Ferastral in doses not inducing maternal toxicity did not adversely affect litter size, foetal loss, litter weight or embryonic or foetal development in eithe

ISSN:0036-553X    

DOI:10.1111/j.1600-0609.1977.tb01218.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY