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Biomedical subjects

D Fernandes

Publications and source records attributed to D Fernandes.

At least 37 records · Page 2Linked to original sources
PubMed1994

Urinary iron excretion depends on the mode of administration of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one in patients with homozygous beta-thalassemia.

OBJECTIVE: To examine the effect of frequency of oral administration of 1,2-dimethyl-3-hydroxypyrid-4-one (L1) on urinary iron excretion. HYPOTHESIS: Sustained serum concentrations of L1 will cause more iron chelation than the same daily dose given in larger but less frequent amounts. PATIENTS AND METHODS: Ten patients with thalassemia with a mean age of 20.9 +/- 4.7 years (range, 13 to 27 years), who were receiving regular treatment with 75 to 100 mg/kg/day oral L1, received 75 mg/kg/day L1 orally in equally divided doses: every 6 hours for 3 days and every 12 hours for 3 days. The two study periods occurred 1 month apart immediately after the monthly blood transfusions. Urine was collected for two consecutive 24-hour periods during each of the different schedules. Serial blood samples were collected from six patients over a 6-hour period and analyzed for total L1 and the L1 glucuronide metabolite concentrations. RESULTS: The patient's mean hemoglobin levels (138.8 +/- 12.5 and 139.0 +/- 11.6 gm/L) and ferritin levels (2856.4 +/- 2207.8 and 2890.0 +/- 2264.4 micrograms/L) were similar during the every-6-hour and every-12-hour L1 administrations, respectively. There was significantly more urinary iron excretion when L1 was administered every 6 hours (0.59 +/- 0.29 mg/kg/day) versus every 12 hours (0.40 +/- 0.26 mg/kg/day; p = 0.0129). Calculated 24-hour area under the plasma concentration-time curve of L1 was similar during the every-6-hour (7023.9 +/- 2637.8 mg.min/L) and every-12-hour (7050.1 +/- 1668.8 mg.min/L) experiments. CONCLUSIONS: These data suggest that the sustained presence of L1 in the blood results in greater chelation of iron than that observed with larger, less frequent doses.

Administration, Oral↗
PubMed1993

Comparison of the pharmacokinetics of 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in healthy volunteers, with and without co-administration of ferrous sulfate, to thalassemia patients.

Given the mortality and morbidity associated with acute iron intoxication, effective iron chelation which is easily administered in an emergency situation would be ideal. The pharmacokinetics of L1 were examined in 5 healthy adult male volunteers to assess its potential for use in acute iron overload. Ferrous sulfate (600 mg), L1 (900 mg), and ferrous sulfate and L1 were administered on three separate days, each one week apart. On each test day, blood samples were collected at regular intervals for the measurement of plasma L1 and total iron. Pharmacokinetic values were calculated. The data were also compared to that obtained in 10 patients with beta-thalassemia and chronic iron overload. In the normal volunteers, a 20% decrease in the area under the concentration time curve of plasma iron and of plasma L1 was demonstrated when they were co-administered. There was no change in urinary iron excretion when L1 was given with iron (p = 0.414). The elimination half-life of L1 in the thalassemia patients (137.65 +/- 48.65 min) was significantly longer than that in the healthy volunteers (77.56 +/- 13.0) (p = 0.0047) due to larger apparent volume of distribution. In all of the iron-overloaded individuals L1 resulted in increased urinary iron excretion. None of the other pharmacokinetic variables compared were significantly different between these two groups. These studies indicate that at levels below saturation, transferrin does not allow L1 to remove absorbed iron in healthy volunteers, whereas in thalassemia patients, who are beyond saturation of their iron binding capacity, the drug binds iron and promotes its excretion.

Adolescent↗
PubMed1992

Therapeutic drug monitoring of retinoids.

Retinoids are natural or synthetic compounds related to vitamin A. They are successfully used in the treatment of dermatological disorders. However, one of the limiting factors in the use of retinoids is their huge teratogenic potential. The investigation into the pharmacokinetics and metabolism of retinoids has encountered many difficulties due to lack of suitable techniques to deal with these labile compounds. Because of the teratogenic nature of the retinoids, the sensitivity of the assay is of utmost importance. We report a systematic comparison between two high-performance liquid chromatographic methods used to monitor levels of etretinate and its metabolites acitretin and 13-cis-acitretin in plasma. Our analysis suggests that the column-switching method is superior owing to smaller variability in results and its simplicity. We also describe our therapeutic drug monitoring program for counseling women of reproductive age following etretinate or acitretin exposure. Presently, labeling of etretinate in North America suggests that women should refrain from conception for an undetermined length of time. Assessment of serum concentrations over time is beneficial in defining the length of period to postpone conception.

Acitretin↗
PubMed1990

Heroin users seeking methadone treatment.

Seven hundred and sixty-seven patients applying to enter public methadone programmes in the western suburbs of Sydney underwent assessment in the Drug and Alcohol Unit at Westmead Hospital between 1986 and 1988. These patients had long histories of illicit drug use and most were involved in crime, prostitution and a drug subculture. Many abused multiple drugs, and almost all had been exposed to hepatitis B virus. However, human immunodeficiency virus (HIV) seropositivity rate was low. Methadone programmes, at least in Sydney's western suburbs, attract a very disadvantaged population for whom rehabilitation is likely to be a difficult, long-term process.

Adult↗