Biomedical subjects

M Bourdeaux

Publications and source records attributed to M Bourdeaux.

22 records · Page 2Linked to original sources

PubMed1982

Study of the interaction between human serum albumin and some cephalosporins.

Dialysis and microcalorimetric methods were used to calculate the binding parameters of some cephalosporins to human serum albumin (HSA) and to study the nature of the interactions involved in the binding process. Dialysis results agree with microcalorimetric data for cephapirin, cephradin, cefamandole, and cefazolin. Binding forces seem to be principally electrostatic. The parts of the drug molecule involved in HSA drug binding have been identified by high-resolution NMR. The major binding site for cephalosporins with high HSA affinity is thought to be the electron-rich heterocyle fixed on the methylene at position 3. Four classes of cephalosporin have been defined: (a) very weak affinity for HSA (cephalexin, cephradin); (b) moderate affinity (cephapirin, cefoxitin, and cefotaxime) in which binding to the protein involves the heterocycle substituent of the acetamide chain carbon atom; (c) strongly binding (cefamandole), in which binding to HSA is by means of the methyltetrazole ring; and, finally (d), cefazolin, with two classes of binding sites for protein, showing strong and moderate affinity.

Calorimetry↗

PubMed1980

Modification of human serum albumin binding of methotrexate by folinic acid and certain drugs used in cancer chemotherapy.

The binding of methotrexate (MTX) and citrovorum factor (CF) to human serum albumin (HSA) was investigated. The affinity constant for MTX was 820 M-1, with 2 binding sites, and for CF 2340 M-1, with 1.5 binding sites. MTX and CF, which are used together in high dose therapy, compete for HSA binding. Competition for HSA binding between MTX and adriamycin, bleomycin and cyclophosphamide, drugs often used in association with MTX in cancer chemotherapy, was also demonstrated. The clinical importance of such competition depends on the drug/protein concentration ratio which is extremely variable.

Antineoplastic Agents↗

PubMed1978

Microcalorimetric method to determine competitive binding. Action of a psychotropic drug (dipotassium chlorazepate) on L-tryptophan . human serum albumin complex.

A mathematical treatment and an original microcalorimetric method are developed to verify an eventual competitive binding between any two substances for the same macromolecule. To apply this method, a competitive binding of L-tryptophan and one benzodiazepin (dipotassium chlorazepate) for human serum albumin is perfectly demonstrated. The association constants and the enthalpy variations are equal to 14 000 +/- 2000 M-1 and --6.6 +/- 0.2 kcal/mol for human serum albumin . tryptophan complex and 13 000 +/- 1000 M-1 and --10.0 +/- 0.2 kcal/mol for human serum albumin . chlorazepate complex. In all cases the stoichiometry is equal to one. The binding of tryptophan to human serum albumin is partially stereospecific; the association constant and the enthalpy variation for D-tryptophan complex are equal, respectively, to 1000 +/- 200 M-1 and --2.6 +/- 0.3 kcal/mol.

Anti-Anxiety Agents↗

PubMedDate not supplied

In vitro plasma binding of some second generation antitumor platinum complexes.

The kinetics of five cisplatin analogs binding to human plasma fractions possessing a molecular weight greater than 50,000 daltons were studied. Each drug solution in plasma ultrafiltrate or phosphate buffer (pH = 7.4, mu = 0.154) was mixed with human plasma and filterable platinum concentrations were measured versus time by atomic absorption spectrophotometry. The only Pt IV compound studied did not bind. All the other Pt II complexes bound, but their binding kinetics were quite different. The experimental data were fitted to a theoretical equation based on the hypothesis that plasma nucleophilic agents possessing a molecular weight greater than 50,000 daltons are able to react with Pt compounds with an apparent second order rate constant. The apparent reaction rate constants and initial concentrations of these nucleophilic agents were calculated. The difference between the respective values obtained for each cisplatin analog could be explained by differences in their chemical formulas. Therefore our result should contribute towards a better understanding of the pharmacokinetics of the cisplatin analogs studied.

Antineoplastic Agents↗