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Biomedical subjects

R Favre

Publications and source records attributed to R Favre.

At least 127 records · Page 7Linked to original sources
PubMed1984

Clinical pharmacokinetics of vindesine: repeated treatments by intravenous bolus injections.

Vindesine was administered intravenously to 12 patients with advanced cancer. Treatment was repeated after 2 weeks or more with a 1.5-to 2-fold increased dose of vindesine. Five patients received one or two additional injections at the higher dose level. One patient was given 0.4, 1 and 4 mg of vindesine on days 1, 3 and 6 and then 8 mg on days 19 and 34. Plasma samples and urine were collected over 3 days after injection and monitored for vindesine by radioimmunoassay. Significant time-dependence of vindesine plasma concentration decay kinetics at a constant dose was observed in four patients out of six. The comparison of the kinetics after administration of different doses to the same patient revealed frequent deviations from linearity with no obvious general trend. Urinary excretion was very low (1-12% of the dose), and urinary excretion rates correlated with plasma concentrations. Renal clearances were variable from one patient to another and also for the same patient from one injection to another. These data were interpreted in terms of time- and dose-dependence of vindesine pharmacokinetics.

Adult↗
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↗
PubMed1984

[Comparison of 2 chemosensitivity tests by grafting a polyoma tumor in the cheek pouch of syngeneic hamsters and under the renal capsule of syngeneic mice].

The immunocompetent subrenal capsule assay tumour graft is a good chemosensitivity test. We have compared it to immunocompetent white hamster cheek pouch tumour graft. These two assays are both easy to perform. Each has specific advantages and disadvantages. However the six days immunocompetent mouse subrenal capsule assay tumour graft is the most practicable and reproducible. The hamster cheek pouch assay would be used when mouse subrenal capsule assay would not be efficient for the molecules under study.

Animals↗
PubMed1983

[Prediction of response to antineoplastic agents].

It now seems possible to predict response to anti-cancer drugs by means of several methods classified into three groups. Methods in the first group are aimed at determining the intracellular mechanisms required for the drugs to act on the tumoral cells; apart from hormone receptor assays, few of these have practical applications. Methods in the second group are concerned with the action of cytostatic drugs on malignant cells; clonogenic cultures and human tumour xenografts in mice are already routinely used. Finally, methods to evaluate the pharmacokinetics of anticancer drugs are being developed. These three groups of methods can be used in the pre-clinical screening of these drugs or at the clinical trial phase to predict individual responses to chemotherapy.

Animals↗
PubMed1983

Immunomodulation by NPT 15392 in cancer patients under chemotherapy.

A clinical trial of NPT 15392, a purine derivative, was run in ten head and neck cancer patients presenting signs of immunosuppression and undergoing repeated chemotherapy. A battery of ten tests was used to assess the immune status of the subjects. Those tests included skin tests, lymphocyte investigations (count, E-rosetting, membrane fluorescence and lymphoblastic transformation) and determination of serum levels of C'3 fraction of complement and IgA. The drug induced transitory, immune stimulation during or after treatment without any side effects. NPT 15392 seemed to selectively exert an action on T lymphocytes. Inasmuch as transitory, immune stimulation and secondary immune depression were noted after treatment, the therapeutic protocol for use of this drug should be reexamined.

Adjuvants, Immunologic↗
PubMed1983

Time dependency of adriamycin and adriamycinol kinetics.

Adriamycin was administered by IV injection to seven patients with various solid tumors at a dose of 30 mg/m2 during successive courses. Extraction was carried out by the SEP-PAK method for plasma and by solvents for urine. Plasma and urinary levels of adriamycin and adriamycinol were determined by high-performance liquid chromatography over 72-h period after injection. Pharmacokinetic parameters for adriamycin and adriamycinol were calculated for each course of treatment. The results show significant inter- and intra-individual variations in the kinetics and elimination of both compounds. The analysis of pharmacokinetic data reveals a wide variability in the fluctuations observed during the successive courses in different patients. This study confirms the time-dependency of ADR kinetics.

Adult↗
PubMed1983

In vitro formation of polyglutamyl derivatives of methotrexate and 7-hydroxymethotrexate in human lymphoblastic leukemia cells.

The intracellular synthesis of polyglutamyl derivatives of both methotrexate (4-amino-N-10-methylpteroylglutamic acid) and 7-hydroxymethotrexate, the primary plasma metabolite of methotrexate in humans, was evaluated in a methotrexate-sensitive, acute lymphoblastic leukemia cell line, MOLT 4. These studies were performed using a highly specific ion-pairing high-pressure liquid chromatography method which permits the simultaneous determination of methotrexate, 7-hydroxymethotrexate, and their corresponding polyglutamyl derivatives. When MOLT 4 cells were exposed to 1 microM methotrexate, the monoglutamate attained a steady state after 30 min, and polyglutamyl derivatives having from one to 4 additional glutamyl residues were observed over 4 hr. Four additional metabolites were also detected upon incubation with 1 microM 7-hydroxymethotrexate. On the basis of the retention times for these compounds relative to methotrexate polyglutamyl standards and since these metabolites reverted to 7-hydroxymethotrexate upon treatment with a preparation of hog kidney conjugase, they were identified as polyglutamyl derivatives of 7-hydroxymethotrexate. The identification of 7-hydroxymethotrexate polyglutamyl derivatives in vitro raises the possibility of an important new dimension in the pharmacological action of methotrexate. We investigated the effect of extracellular 7-hydroxymethotrexate on net methotrexate uptake and metabolism when cells were exposed simultaneously to 1 microM [3H]-methotrexate and unlabeled 7-hydroxymethotrexate. A decrease in the levels of both intracellular methotrexate and the corresponding polyglutamyl derivatives was noted for cells treated with 1 or 10 microM 7-hydroxymethotrexate. However, no appreciable effect of 7-hydroxymethotrexate on the amount of polyglutamyl derivatives formed relative to the total intracellular antifolate was noted. These studies show that in MOLT 4 cells (a) both methotrexate and 7-hydroxymethotrexate are rapidly converted to polyglutamyl derivatives, and (b) 7-hydroxymethotrexate interferes with net methotrexate accumulation and metabolism when present simultaneously in the extracellular medium. These results, moreover, suggest a potential role for 7-hydroxymethotrexate in modulating the biochemical effects of methotrexate in vivo.

Cell Line↗
PubMed1982

[Immunologic assessment and acoustic "stressing situation" in an experimental system BALB/c mice, the Tsc-3T3 tumor].

Previous results in Hamsters showed enhancement of tumor takes in animals exposed to acoustic aggression. Since this phenomenon could be due to immunodepression, we investigated whether this was the case in a better defined system of inbred BALB/c Mice. The results show that in these conditions, the tumor graft could not transgress a minor histocompatibility antigen nor decrease the protective effects of polyoma virus against tumor challenge and that all the immune tests investigated were unaltered.

Acoustic Stimulation↗
PubMed1982

Maintenance chemoimmunotherapy of nonlymphoblastic acute leukemias.

A trial of maintenance chemotherapy of nonlymphoblastic acute leukemia led to a comparison of two groups of patients in complete remission. Group 1 (14 patients) received only monthly reinduction chemotherapy. Group 2 (17 patients) received identical chemotherapy together with weekly immunotherapy combining BCG and irradiated leukemic cells. While the duration of the first complete remission was unmodified, the overall survival time and, above all, survival after the first relapse were prolonged in group 2 chemoimmunotherapy. These results were all the more marked when a homogeneous group of patients having received the same induction chemotherapy were considered.

Adolescent↗
PubMed1982

High-dose methotrexate: a clinical and pharmacokinetic evaluation. Treatment of advanced squamous cell carcinoma of the head and neck using a prospective mathematical model and pharmacokinetic surveillance.

Some of 66 patients with head and neck tumors were treated with high-dose methotrexate monochemotherapy. The use of a prospective mathematical model with pharmacokinetic surveillance proved to be reliable, practical, and useful. By this means chemotherapy could be individualized, with a resultant marked reduction in the frequency and severity of toxicity. The onset of clinical toxic manifestations was significantly correlated with a poor therapeutic response and poor prognosis. The patients were classified in to three groups according to poor, intermediate, and good pharmacokinetic parameters calculated after an intravenous identification dose of methotrexate. These group allocations had a very high prognostic value with regard to toxicity, and especially to the quality of therapeutic response to high-dose methotrexate. They are suggested as useful guidelines in the prescription of high-dose methotrexate chemotherapy.

Adult↗
PubMed1981

Genetical and structural analysis of a group of lambda ilv and lambda rho transducing phages.

Eight lambda ilv C transducing phages generated from E. coli K12 secondary site lysogens have been analysed genetically and physically. Two of them carry, in addition, the rho gene and its promotor region, but not the cya gene. The ilv O 603 mutation has been located between ilv G and ilv E. Electrophoretic analysis of the proteins synthesized by these phages in a system of UV irradiated cells allowed us to assign molecular weights of 55000 and 66000 daltons to the ilv C and the ilv D gene products, respectively, and to show that an ilv G-encoded polypeptide of 60000 daltons is made from an ilv O- but not from an ilv O+ phage. The expression of the ilv G gene is discussed in the light of the recent finding of a promoter-attenuator region lying upstream to ilv G. Finally, we have found that one of the lambda ilv phages does not have the classical structure of a transducing phage.

Amino Acids, Branched-Chain↗
PubMed1981

[Polytraumas].

Explore the source record for details and available documents.

Humans↗
PubMed1980

[Composite lymphoma. Review of the literature].

The authors report of a case of composite lymphoma, defined by the coexistence of two clearly different types of malignant lymphoma in a single lymph node or splenic site. A review of the literature led to the discovery of 20 cases of this type of lymphoma. The macroscopic and histological lesions are analysed.

Adult↗
PubMed1979

[Non-lymphoblastic acute leukaemia: maintenance therapy by trial of a combination of chemo- and immunotherapy (author's transl)].

A trial of immunotherapy in the maintenance treatment of non-lymphoblastic acute leukaemias led to a comparison of 2 groups of patients in complete remission. Group C (14 patients) received only monthly reinduction chemotherapy. Group C + I (17 patients) received identical chemotherapy together with weekly immunotherapy combining BCG and irradiated leukaemic cells. Whilst the duration of the first remission was unmodified, the overall survival and above all survival after the first recurrence were prolonged in group C + I. These results were all the more marked when a homogeneous patients having received the same induction chemotherapy is considered.

Acute Disease↗
PubMed1979

High-dose methotrexate: preliminary evaluation of a pharmacokinetic approach.

Clinical pharmacologic studies have been carried out in patients with head and neck tumors following 36-h continuous infusions of high-dose MTX (1.5 g/m2). The results indicated considerable variation in the amount of MTX in the blood of individual patients. To control these variations, a modified protocol was set up to try to attain the same MTX blood level in all subjects. The protocol has a pharmacokinetic basis and involves determination of the MTX kinetics in each patient. The information thus obtained allows us to compute a 36-h infusion dose so that the MTX plasma levels never exceed a threshold beyond which there is a risk of toxicity to the host. The computation is validated by taking a blood sample 6 h after the beginning of the infusion. If the MTX concentration is higher than its expected value, the infusion rate can then be immediately reduced. Analytical methods that will allow such a computation, the results of the clinical application of this pharmacokinetic approach, and some implications of such a method are discussed.

Aged↗