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Biomedical subjects

M Lecomte

Publications and source records attributed to M Lecomte.

42 records · Page 3Linked to original sources

Protein-bound and free plasma phenytoin during pregnancy.

In a clinical study using low doses of phenytoin as an ovulation inducer, the plasma levels and the binding percentages of this drug and the plasma level of its main metabolite, p-hydroxyphenytoin, were monitored. The results show that during pregnancy, plasma levels of both remain stabile and low as compared with those observed in epilepsy treatment. This could be one explanation for the absence of teratogenic effects observed in this and other studies using phenytoin for the same therapeutic aim.

Blood Proteins↗

Binding of digitoxin, digoxin and gitoxin to human serum albumin.

The binding of three digitalis glycosides, digitoxin, digoxin and gitoxin, to human serum albumin was studied in vitro by equilibrium dialysis. The results obtained showed that binding is a non saturable process and that probably the same binding mechanism is involved for each of the three drugs. Their binding sites seem to be different from of those of acidic and basic drugs. However, the three drugs were found to be partially displaced by large amounts of fatty acids.

Digitalis Glycosides↗

Phenytoin binding to human albumin.

Binding of phenytoin to human plasma proteins and to human serum albumin is studied using equilibrium dialysis method at pH 7.4 and 37 degrees C. Phenytoin is mainly bound to albumin, the percentage of bound drug being constant over a wide range of total drug concentrations. Calculation of the drug binding parameters show a low affinity, k = 745 M-1, and a high number of binding sites, n = 8. Palmitic acid and some acidic drugs, warfarin and phenylbutazone added to human serum albumin, decreased phenytoin binding in a non competitive way. Basic and non-ionizable drugs, on the other hand, did not modify phenytoin binding.

Anilino Naphthalenesulfonates↗

Importance of 5-fluorouracil dose-intensity in a double randomised trial on adjuvant portal and systemic chemotherapy for Dukes B2 and C colorectal cancer.

366 patients fully resected from a Dukes B2 or C colorectal cancer were randomised to receive 6 courses of systemic chemotherapy comprising either 5-fluorouracil (5 FU) alone (arm A: 450 mg/m2/day-5/21 days) or combined folinic acid (FOL) and 5 FU (arm B: respectively 200 mg/m2 racemic form or 100 mg/m2-l-form and 370 mg/m2/day-5/21 days). 173 patients had also been initially randomised to receive one course of intraportal chemotherapy just after surgery or no portal treatment. Oral levamisole (150 mg/day; 3 days every other week) was given to all patients for one year. A significantly higher incidence of leuco-granulocytopenia was observed in the arm A (5 FU alone) inducing more frequent dose delays and adaptations as well as levamisole's withdrawal. Then dose-intensities and dose-intensity products were lower in this arm but the dose intensity expressed in mg/m2/week remained higher (631 +/- 107 vs 557 +/- 99; p < 0.001). The median follow-up in the study was 4.5 years. Relapse free (RFS) and overall survivals (OAS) were prolonged in the 5 FU alone group peculiarly in those patients who had not been randomised for portal treatment. Curves diverged progressively with longer follows-up (at 8 years; RFS in arm A: 67-71% vs 59-53% in arm B; OAS in arm A: 72-74% vs 56-46% in arm B). Patients suffering from a colon or a Dukes C cancer benefited the most from the treatment with 5 FU alone. The results are discussed in the light of other recent adjuvant trials. Well dosed 5 FU over a short period of time without folinic acid may be a valuable and inexpensive adjuvant treatment for colorectal cancer. Levamisole may no longer be recommended in this setting.

Adjuvants, Immunologic↗

Levamisole adds granulocyte toxicity to 5FU-based chemotherapies in adjuvant treatment of Dukes B-C colorectal cancer. A preliminary report.

41 patients (pilot study-I) and 50 patients (multicenter study II) were randomized to receive as systemic chemotherapy for 6 courses with 5 FU alone (A) [440 (I)-450 (II) mg/m2 IV bolus, 5/21 days] or folinic acid followed by 5 FU (B) (respectively 200 and 370 mg/m2 IV bolus, 5/21 days). In the multicenter trial, oral levamisole at the dose of 150 mg/day (3/14 days) was added to chemotherapy for one year. Ten patients in study I and 19 patients in study II also received a post-operative course of intra-portal chemotherapy. Toxicity was evaluated respectively on 232 (I) and 276 (II) courses. Clinical limiting toxicities were stomatitis and diarrhea. In protocol II, a significant enhancement of grades 3-4 granulocyte toxicity was seen (17.3% of courses in II vs only 3.4% in I; p < 0.001). This was especially recorded in the group treated with 5-FU alone (26% of courses in A vs 11% in B; p < 0.001). Levamisole was therefore stopped in 12 cases (10 cases in A; 2 cases in B).

Aged↗