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Biomedical subjects

R Gilli

Publications and source records attributed to R Gilli.

28 records · Page 2Linked to original sources
PubMed1984

Assay of methotrexate and 7-hydroxymethotrexate by gradient-elution high-performance liquid chromatography and its application in a high-dose pharmacokinetic study.

A paired-ion high-performance liquid chromatographic method is described for the simultaneous determination of methotrexate (MTX) and its major metabolise, 7-hydroxymethotrexate (7-OH-MTX), in plasma and urine. In addition, this technique permits the separation of other known metabolites of MTX, such as DAMPA and MTX-polyglutamates. After selective extraction on an anion-exchange resin column, both compounds and the internal standard, aminopterin, were separated on a reversed-phase octadecylsilane column with UV-detection at 313 nm. The detection limits for plasma and urine samples were approximately 40 ng/ml (8.8 x 10(-8) M) for MTX and 100 ng/ml (2.1 x 10(-7) M) for 7-OH-MTX. This method was applied in pharmacokinetic studies following 24-h infusion of high-dose MTX in four patients during two successive treatments. After the end of the infusion, the mean apparent half-life for the metabolite was 19.1 h, while that for MTX was 8.8 h. A stepwise increase in the plasma concentrations of both MTX and its metabolite was observed during the second MTX infusion. This increase was reflected in the cumulative urinary excretion of both drug and its metabolite.

Journal Article↗
PubMed1983

Interaction of methotrexate metabolites with beef liver dihydrofolate reductase-I. Binary complex study.

In order to explain the difference of inhibition of dihydrofolate reductase (DHFR) by methotrexate (MTX) and its metabolites 7-hydroxymethotrexate [7OH (MTX)] and polyglutamate derivatives [MTX (G1) and MTX (G2)], direct determinations of binding parameters to beef liver DHFR were performed. Association constants are calculated by fluorescence titrations and thermodynamic parameters by microcalorimetric measurements. The parameters of interaction are nearly identical for MTX and polyglutamate derivatives but are different for MTX and 7OH (MTX). For this last derivative electrostatic forces are less predominant and a larger modification of its conformation appears in the enzyme during the complex formation.

Animals↗
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↗
PubMed1981

Advantages and limitations of pharmacokinetic studies in the rationalization of anticancer therapy: methotrexate and 5-FU.

The use of pharmacokinetic studies for individual dose regimen adjustments in anticancer therapy is considered. The example of methotrexate in the treatment of head and neck tumors demonstrates the validity of this approach. Moreover, the importance of biotransformations of this antimetabolite is confirmed using a high pressure liquid chromatography assay. The example of 5-FU outlines the analytical and mathematical difficulties rendering this approach unlikely for routine use. Some preliminary relations between pharmacokinetic parameters (plasma clearance) and clinical response are presented. The determination of the main plasma metabolic 5-6 dihydro 5-FU by GC/MS and its possible role in the nonlinear pharmacokinetics of the drug in therapeutic failure are discussed.

Drug Administration Schedule↗
PubMedDate not supplied

Adoptive immunotransfer with viable donor mononuclear cells for recurrent chronic myelogenous leukemia after allogeneic bone marrow transplantation in two children.

Two children with Ph+ chronic myelogenous leukemia (CML) relapsed in the chronic phase after allogeneic bone marrow transplantation (BMT). They were treated with transfusions of peripheral blood mononuclear cells (PBMC) obtained from the former bone marrow donors in combination with interferon alfa-2. In one child, CML was successfully controlled as shown by disappearance of Ph+ metaphases as well as negativity for BCR-ABL fusion gene transcripts demonstrated by polymerase chain reaction (PCR) analysis. The patient has remained in complete remission without evidence of disease for 12 months after donor PBMC transfusions. The other child showed disappearance of BCR-ABL gene transcripts by PCR analysis only in peripheral blood cells, but PCR positivity persisted in bone marrow samples. These results indicate that adoptive immunotherapy may be a further alternative in children with relapse of CML after allogeneic BMT as previously described for adult patients.

Adolescent↗