Biomedical subjects
I Lucas
Publications and source records attributed to I Lucas.
Comparison of intravenous and oral high-dose methotrexate in treatment of solid tumours.
An outpatient regimen of oral high-dose methotrexate was studied in 14 patients with solid tumours over 12 months. Detailed pharmacokinetic analysis in five patients showed high oral bioavailability (mean +/- SE of mean 87.6 +/- 1.5%), indicating that with this regimen oral methotrexate was well absorbed and the first-pass effect low. Oral administration resulted in peak plasma methotrexate concentrations of 8.4 +/- 0.5 mumol/l (382 +/- 23 microgram/100 ml) and was almost as effective as intravenous administration, which achieved peak concentrations of 9.9 +/- 0.4 mumol/l (450 +/- 18 microgram/100 ml). In all 14 patients the clinical response to oral treatment was comparable to that reported to intravenous administration of high-dose methotrexate used in combination with other cytotoxic drugs. The disease-free interval in cases of adult sarcoma was 7.4 +/- 1.3 months and the relapse rate 29%. Out of four patients with small-cell carcinoma, two showed an objective response to oral treatment. We suggest that oral high-dose methotrexate given in divided doses is a rational alternative to expensive intravenous high-dose methotrexate regimens, but further clinical evaluation is necessary.
Ocular side effects with 5-fluorouracil.
The concentrations of 5-fluorouracil in tears and plasma were studied in eight patients receiving the drug for carcinoma of the colon. The drug was measured by a gas liquid chromatographic method and found to be present only in the tears of patients with excessive lacrimation. In three patients with watery eyes the peak concentration in tears (16-23.8 micrograms/ml) occurred 15 minutes after IV administration and this corresponded with the end of the distribution (alpha) phase in the plasma when the plasma levels ranged from 18-26 micrograms/ml. In five patients without eye symptoms the drug was undetectable in the lacrimal fluid even though they had similar plasma levels (15-25 micrograms/ml) of 5-fluorouracil. The volumes of distribution and plasma clearance rates were similar in the two groups [being 0.2-0.52 (mean = 0.33) 1/kg and 612-978 (mean = 850) ml/min respectively in patients with excessive lacrimation and 0.13-0.79 (mean = 0.36) 1/kg and 435-1138 (mean = 831) ml/min respectively in the five patients without symptoms.]. It appears that 5-fluorouracil produces irritation of the lacrimal apparatus in about 30% of patients on the drug and in association with this appears in the tears where it may be responsible for the reported irritation and fibrosis of the tear duct.
[A clinical report. Atypical subacute thyroiditis].
We present a patient 52 years old with a symtomatology of three month's evolution with: rapid weight loss, weakness in legs fasciculated tremor increased by any physical effort, nervousness and anxiety. The isotopic exploration of thyroid in basal conditions and after estimulation with TSH shows a very small captation of iodide. The determination of T 4 shows a notable increase (24 U. U. Normal range is 7,5 to 10,5 U. U.). The clinical symtomatology biochemical and gammagraphic datum support the diagnostic of subacute thyroiditis and also the posterior evolution of symtomatology in spite of the absence of odynophagia and the increase of syze of the thyroid. We comment on the particularity of this clinical entity that could be confused with thireotoxicosis because of its atypical character of presentation.
Lacrimation and 5-fluorouracil.
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Fluorouracil therapy in patients with carcinoma of the large bowel: a pharmacokinetic comparison of various rates and routes of administration.
The pharmacokinetics of fluorouracil after oral, intravenous and rectal administration were compared in 12 patients with colorectal cancers. Oral administration of 10 to 15 mg/kg gave variable plasma levels (0 to 10.5 microgram/ml) and bioavailability (0 to 74%; mean 28%). Bioavailability increased markedly with increases in dose, suggesting saturation of the 'first pass' hepatic metabolism of the drug. Differences in bioavailability could not be related to standard liver function tests or the presence of metastatic deposits in the liver. Plasma levels were not detectable after rectal administration in the 4 patients studied and were very low (0 to 8 microgram/ml) during high dose (20 to 30 mg/kg/24h) slow intravenous infusion in 6 patients. These findings indicate that different dose schedules and routes of administration produce markedly different plasma levels. They suggest that the rate of degradation of fluorouracil by the liver is quite variable and may become saturated with increasing dose. For these reasons monitoring of plasma levels of the drug in individual patients may be useful.