A N Bartlett

University of London, Londinium, England, United Kingdom

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Publications (7)56.5 Total impact

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    ABSTRACT: The oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1, deferiprone, CAS 30652-11-0) has been given daily for 3-11 months to 6 transfusion dependent iron loaded patients (myelodysplasia (MDS) 2, Diamond-Blackfan anaemia 1, thalassaemia intermedia 1, thalassaemia major 2). Daily doses of 3 g, 2 x 2 g and 3 x 2 g were administered for the first 2-7 months. Daily doses of 2 x 3 g were also used for periods up to 4 months. Urine iron excretion following 3 g of L1 was found to be related to the number of previous transfusions but not to serum ferritin or the amount of L1 excreted. In each case 24 h urinary iron excretion in response to 3 g L1 ranged from 5-21 mg in MDS, 13-25 mg in a thalassaemia intermedia and a Diamond-Blackfan patient and 16-110 mg in thalassaemia major patients. Further increases of urinary iron were observed in all the patients when the daily dose was increased. Serum ferritin levels have fluctuated but overall have remained unchanged. Biochemical assessment did not show any major abnormalities ascribed to L1 except from subnormal serum zinc levels in two patients and white blood cell absorbate in another. In a separate study we have compared urinary L1 and iron excretions in 7 transfusional iron loaded patients. In all the cases the concentration of L1 was in excess of iron and higher than the level required for 100% iron binding. There was no other apparent correlation between the concentrations of L1 and iron in the urines studied.(ABSTRACT TRUNCATED AT 250 WORDS)
    Arzneimittel-Forschung 02/1995; 45(1):65-9. · 0.56 Impact Factor
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    ABSTRACT: 1,2-Dimethyl-3-hydroxypyrid-4-one (L1) has been given daily for 1-15 months to 13 transfusion dependent iron loaded patients. No significant change occurred in liver, renal or cardiac function, ECG and radionucleotide angiocardiogram, in audiometry tests and in visual function and electrical retinography. No skin rashes, gastrointestinal symptoms and no neurological changes that could be detected clinically were observed. Two of the patients died of their underlying diseases. One patient had severe cardiac abnormalities before receiving L1 and died of congestive heart failure with infections 5 weeks after stopping a 2-month course of L1. The other, a patient with myelodysplasia suffered recurring infections due to progression of the disease. Joint and muscle pains occurred in five patients. In two these disappeared despite continuing the drug; another patient developed swollen ankle joints which gradually resolved on stopping L1 therapy; a patient with underlying osteoarthritis complained of mild pain and stiffness in her knees which remained intermittent both on and off the drug while in the fifth patient peripheral small joint swelling and pain present before starting L1 improved with L1 therapy. One patient, with Blackfan Diamond anaemia, developed a Lw red cell antibody 6 months after commencing L1. This disappeared on stopping the drug and did not reappear. She then developed severe agranulocytosis and thrombocytopenia 6 weeks after recommencing L1 after 3 months discontinuation of the drug. No other patient showed a change in granulocyte or platelet count.
    British Journal of Haematology 11/1990; 76(2):301-4. · 4.94 Impact Factor
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    ABSTRACT: A long-term clinical trial of 1-15 months has been carried out with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in 13 transfusion-dependent iron-loaded patients. Urinary iron excretion was greatest in patients with thalassaemia major and was related to the number of previous transfusions but not to the serum ferritin level. Substantial increases of urinary iron were observed in all the patients when the frequency of the daily dose was doubled and in response to 2 x 3 g L1 daily 11 of 12 patients tested excreted greater than 25 mg iron daily, the mean daily intake of iron from transfusion. Serum ferritin levels have fluctuated but overall have remained unchanged. Pharmacological studies in five patients have indicated rapid absorption probably from the stomach and variable plasma half life of 77 +/- 35 min (X +/- SD). Glucuronation was identified as a major route of L1 metabolism. Short-term intensive chelation studies using repeated administration of L1 resulted in further increases of urinary iron excretion by comparison to a single dose. In one case 325 mg of iron were excreted in the urine following the administration of 16 g (5 x 2 g + 2 x 3 g) within 24 h. Iron excretion studies were carried out in six transfusional iron-loaded patients who were maintained on a low iron diet before and during chelation. No significant increases of faecal iron excretion were observed with L1 using daily doses of up to 3 x 3 g and 4 x 2 g. The high level of compliance during treatment with L1 and the levels of urine iron excretion that can be achieved increase the prospects for oral chelation in transfusional iron-loaded patients.
    British Journal of Haematology 11/1990; 76(2):295-300. · 4.94 Impact Factor
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    ABSTRACT: Pharmacokinetic studies have been carried out with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). HPLC analysis of serum of a normal volunteer and seven transfusional iron loaded patients who ingested a 3 gm dose of L1 revealed that L1 was most probably absorbed from the stomach and was transferred to the blood with a half-life of 0.7 to 32 minutes. L1 reached maximum concentration in the serum 12 to 120 minutes after administration with 85% to 90% elimination within the first 5 to 6 hours, with a half-life of 47 to 134 minutes. L1 and its glucuronide metabolite were identified in serum and urine but not in feces. In most cases hydrolysis of 24-hour urine samples with use of beta-glucuronidase resulted in almost complete recovery of the administered dose. Urinary iron excretion was proportional to the iron load but not to the serum or urine concentration of L1. The therapeutic efficiency of L1 can therefore be improved by repeated administration of 2 to 3 gm doses at least every 6 hours.
    Clinical Pharmacology &#38 Therapeutics 10/1990; 48(3):255-61. · 6.85 Impact Factor
  • British Journal of Haematology - BRIT J HAEMATOL. 01/1990; 76(2):295-300.
  • The Lancet 09/1989; 2(8660):457. · 39.21 Impact Factor
  • Progress in clinical and biological research 02/1989; 309:107-14.