Search PubMed⌕ Search

Biomedical subjects

R Favre

Publications and source records attributed to R Favre.

At least 109 records · Page 6Linked to original sources
PubMed1987

Methotrexate test-dose protocol in the presence of 7-hydroxy-methotrexate.

Methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) plasma concentration-time curves (AUC) have been analyzed in 24 patients after different routes of MTX administration. After an i.v. bolus (50 mg/m2), the AUC for 7-OH-MTX is correlated with that for MTX and inversely correlated with the MTX plasma clearance. When MTX is administered with plasma steady level standardization, using the test-dose protocol, at a level of 10(-5) M over 36 hr (10(-5), 36 hr), 7-OH-MTX-AUC is still correlated with the i.v. bolus pharmacokinetic parameters. The dose prediction using the classical test-dose protocol provides a less efficient MTX dose adjustment at 5 X 10(-4) M over 8 hr (5.10(-4), 8 hr) and the hydroxylation process is no more correlated with the i.v. parameters. On the opposite, upon 6 successive infusions with 10(-5), 36 hr or 5.10(-4), 8 hr protocols, the plasma concentrations of 7-OH-MTX are not significantly modified. This suggests that the hydroxylation process is not inducible.

Adolescent↗
PubMed1987

[Anthracyclines in the treatment of epidermoid cancers: uterine cervix, esophagus, bronchi, head and neck].

Anthracyclines certainly do not play a leading role in the treatment of squamous-cell carcinomas. Their effectiveness in these malignancies is limited. In carcinomas of the uterine cervix, variable therapeutic (partial or complete) response rates ranging from 0% to 25% have been reported with doxorubicin as single drug therapy. Using combination chemotherapy, maximum response rates of 54% with cis-platinum and 66% with methotrexate have been achieved. In esophageal carcinoma, a low response rate, fairly consistent across studies, approximating 18%, has been recorded with doxorubicin alone. More satisfactory, although still mediocre results have been recorded with combination chemotherapy, e.g. 33% with FAP (doxorubicin, fluoro-uracile, cis-platinum). Only addition of VP 16 to FAP has yielded a good response rate (66%) in one study. In carcinoma of the lung also, doxorubicin alone has yielded low response rates, approximating 18%. Widely variable results have been reported for the numerous combination chemotherapy trials, with therapeutic response rate ranging from 5% to 66% and mean survivals ranging from 3 months for the least satisfactory trials to 18 months for the few more satisfactory series. In carcinomas of the head and neck, therapeutic response rates with doxorubicin alone have been 20 to 25%. With combination chemotherapy, rates exceeding 50%, occasionally by a fairly wide margin, have been achieved. However, the clinical response may be of fairly short duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibiotics, Antineoplastic↗
PubMed1986

Methotrexate-vindesine association in head and neck cancer: modification of methotrexate's hydroxylation in presence of vindesine.

High-dose methotrexate (HD-MTX) infusions associated with vindesine (VDS) have been used in the treatment of head and neck cancer. In a previous study, VDS was shown to increase the apparent plasma clearance of MTX. We have studied the MTX hydroxylation process in the presence of VDS. Different routes of administration have been tested (IV pushes and 24-h or 36-h infusions). A radioimmunoassay has been developed to measure 7-OH-MTX. The defined protocols enabled us to show that VDS influences not only the pharmacokinetic behavior of methotrexate but also its hydroxylation, which is decreased in presence of VDS.

Adult↗
PubMed1986

Free and conjugated 3,4-dihydroxyphenylacetic acid and homovanillic acid in brain dopaminergic areas at basal state and after pipotiazine activation.

We have determined free and conjugated 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in discrete brain areas of rats. Conjugated HVA or DOPAC accounted for 22-38% of total acids in striatum, mesolimbic tissue or prefrontal cortex. Activation of dopamine (DA) metabolism by a single injection of pipotiazine palmitic ester (PPZ), a long-lasting neuroleptic, increased free acid levels (DOPAC and HVA) at either dose and conjugate levels after 32 or 50 mg/kg. 48 hours after PPZ-32 mg/kg, the observed increases of conjugates could exceed in some cases those of corresponding free acids. About half of total DOPAC and HVA were conjugated in hypothalamus, PPZ moderately increased free DOPAC (at 32 mg/kg) but did not elevate significantly the conjugated form. It is concluded that sulfation is an important pathway for DOPAC and HVA metabolism in brain and that the determination of both free and conjugated DOPAC or/and HVA may shed additional lights on regional DA metabolism and the effect of drugs thereon.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Peripheral distribution of free dopamine and its metabolites in the rat.

Free dopamine (DA) and its metabolites, homovanillic acid (HVA) and 3-4 dihydroxyphenylacetic acid (DOPAC), have been measured and compared with norepinephrine (NE) concentrations in rat peripheral tissues using high performance liquid chromatography with electrochemical detection (HPLC-ED). Detectable amounts of DA and its metabolites were found in all the analyzed tissues. The highest levels were found in carotid body, sympathetic ganglia, urogenital tract and heart, the lowest in liver and lung. DA and DOPAC distribution was heterogeneous and unrelated to NE concentration. Both the variable value of the DA/DA+NE ratio and the presence of DA metabolites in peripheral tissues indicate that a portion of DA may be stored outside noradrenergic neurons and directly catabolized in specific DA pools.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

6-day subrenal capsule assay (SRCA) as a predictor of the response of advanced cancers to chemotherapy.

The 6-day subrenal capsule assay (SRCA) chemosensitivity prediction test using fresh human tumor xenografts was performed in BALBc mice for 80 advanced cancer bearing patients. Among 97 SRCA, nine were non-evaluable because patients either received no chemotherapy or non-assayed drugs, and 12 were non-interpretable because of inadequate control growth. One hundred and six correlations were established between test results and clinical response, 56 retrospective (chemotherapy then test) and 50 prospective (test then chemotherapy). Among the 56 retrospective correlations there are 45 true negative (-/-) and three false positive (+/-) corresponding to 48 poor clinical responders; and eight true positive (+/+) and 0 false negative (-/+) corresponding to eight good clinical responders. Among the 50 prospective correlations there are 26 true negative (-/-) and four false positive (+/-) corresponding to 30 poor clinical responders; and 19 true positive (+/+) and one false negative (-/+) corresponding to 20 good clinical responders. In total among the 106 correlations there are 98% good negative correlations and 79% good positive correlations. The SRCA is practicable and is available for routine clinical use providing results relevant to cancer site and reflecting previous treatment status.

Animals↗
PubMed1986

[Pre and postoperative chemotherapy of osteosarcoma with an adriamycin-cisplatin combination. Risks of a neoadjuvant chemotherapy which is not sufficiently effective].

The authors evaluated a new protocol of neoadjuvant chemotherapy for osteosarcoma, easier to manage and different from T10. The good results obtained with the postoperative ADR-CDDP association led us to undertake a pilot study between 1982 and 1984, using ADR-CDDP as preoperative chemotherapy. The records of sixteen patients were available for follow-up. The average age of the patients was 19.9 years. Patients received two or three preoperative courses, and a total of six identical courses. Tolerance was good. Pain usually disappeared but this was often misleading because associated with radiological and/or clinical tumor progression, low histological necrosis or poor outcome. The continuous disease-free survival actuarial rate was less than 57 and 40% at 18 months and two years respectively. The actuarial survival rate was 87% at one year and 65% at two years respectively. Disappointing results of this preoperative protocol, compared to results with the SO4 78 or T10 protocols for example, led to publish these data early in order to underline their potential dangers. As a result, we stopped our study. The charter of pilot studies justifies this publication. As well, these data point out the necessity of very close follow-up of neoadjuvant chemotherapy by sophisticated medical imaging. Neoadjuvant chemotherapy, if ineffective, must be stopped early, and should lead to surgery, followed by adequate postoperative chemotherapy.

Adolescent↗
PubMed1985

The dynamics of dopamine metabolism in the rat superior cervical, coeliac and mesenteric ganglia.

Dopamine (DA) metabolism was compared in rat superior cervical ganglion, coeliac ganglion, mesenteric ganglion and adrenal medulla. Substantial amounts of DA, 3-4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were found in all the above structures. The proportion of DA metabolites over total adrenergic compounds increased from the superior cervical (22 +/- 2.2%) to the mesenteric ganglia (37 +/- 1.4%) and was much higher in ganglia (30 +/- 1.6%) than in adrenal medulla (1.1 +/- 0.3%). The turnover rates of DOPAC and HVA were calculated in sympathetic ganglia after pargyline (75 mg/kg i.p.) or probenecid (200-500 mg/kg i.p.). After pargyline, the DOPAC levels decreased faster than HVA levels in all ganglia. The corresponding half-lives and calculated turnover rates were: about 4 and 10 min and 100 and 40 pmol/mg protein per h for DOPAC and HVA respectively. No differences were observed between the three ganglia. After probenecid, DOPAC accumulated in all the ganglia in a dose-dependent way; HVA accumulated in the superior cervical and coeliac ganglia but not in the mesenteric ganglion. As in central areas, the turnover rates of DOPAC and HVA calculated on the basis of the greatest accumulation of acidic levels after probenecid were much smaller than those obtained after pargyline. Probenecid increased DOPAC levels in adrenal medulla, but the concomitant changes in DA and epinephrine (E) amounts suggest that probenecid was able to enhance adrenomedullary activity.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

The T4 mot protein functions as part of a pre-replicative DNA-protein complex.

Middle-mode RNA synthesis in T4-infected cells takes place before replication of phage DNA commences. What distinguishes it from early-mode RNA synthesis is that initiation of middle RNA depends on T4-coded proteins, in particular on the mot gene product. mot protein is localized in a DNA-protein complex which forms during the first few minutes of infection. All of the cell's mot protein is bound in this complex, and it continues to be bound long after the synthesis of mot protein has stopped. When we infect Escherichia coli with T4 carrying a temperature-sensitive mutation in the mot gene, we find a correlation between the physiology of this mot mutant and the amount of mot protein bound in the DNA-protein complex. Although there is some host RNA polymerase in the complex, mot protein does not seem to bind to this enzyme. Two other T4-coded proteins, of molecular weights 17,600 and 15,000, are also found in the pre-replicative DNA-protein complex. One of these, p17,600, is coded for by a 750-base pair region located between genes 39 and 56; p17,600 appears to be the recently described motB gene product. The other protein, p15,000, is not an RNA polymerase-binding protein; it is characterized by its strong binding to the DNA-protein complex.

DNA Replication↗
PubMed1985

Bayesian estimation and prediction of clearance in high-dose methotrexate infusions.

Much attention has been paid to the problem of estimating the pharmacokinetic parameters of individual patients in order to optimize dosage choices. Individual kinetics determined by test-dose bolus injection are a basis for predicting drug concentrations after high-dose methotrexate infusion and for computing appropriate dosages. Simplifications may be attempted, even allowing the test-dose to be omitted by using Bayesian estimation rather than likelihood estimation. To individualize pharmacokinetic parameters, Bayesian estimation combines information about population characteristics and those of individuals based on few measured plasma levels during high-dose infusion. Application of this procedure to methotrexate reveals interesting predictive performances and ability to handle variation due to intraindividual time variability without using test doses. The methodology promises to be more efficient in computing dosages in order to avoid toxic levels and will be less expensive in routine clinical use.

Aged↗
PubMed1985

Dosage predictions in high-dose methotrexate infusions. Part 1: Evaluation of the classic test-dose protocol.

A preliminary methotrexate (MTX) kinetic evaluation following administration of an IV bolus (test-dose) allowed individualization of high-dose infusions (HD-MTX). This approach combined with therapeutic drug monitoring was found to have good performance over a large scale of predicted steady-state levels (Css) (10(-5) to 10(-4) M over 24 to 36 h) corresponding to 17 to 650 mg/h deliveries (root mean squared error : rmse (precision) = 1.54 X 10(-5) M (21.4%) and mean error : me (bias) = 0.043 X 10(-5) M (NS)). However a significative (p less than 0.05) but rather low over-estimation of dosage (me = 7.38 X 10(-5) M (14.8%)) associated to a decrease in the prediction precision (rmse = 13.3 X 10(-5) M (26.6%)) occurred in 5 X 10(-4) M predicted Css over 8 h (970 to 1970 mg/h deliveries). However in a number of cases (6 out of 29) important deviations from predicted Css occurred, implying the need to stop the infusion before 8 h. These results indicated that MTX pharmacokinetics was linear from low test-dose bolus injections to high-dose infusions. This allowed dosage predictions based upon preliminary estimation of MTX clearance and associated to therapeutic drug monitoring during and following infusion.

Head and Neck Neoplasms↗
PubMed1985

Dosage predictions in high-dose methotrexate infusions. Part 2: Bayesian estimation of methotrexate clearance.

Population pharmacokinetics of methotrexate (MTX) was evaluated from intravenous test-dose (TD) data (n = 20 corresponding to 174 measured samples). Bayesian prediction of MTX clearance from TD experiments combining population data with measured levels (at times 0.5 and 6 h) was found to be feasible in routine situations with good performance (root mean squared error : rmse (precision) = 1.14 1.h-1 (11.2%) and mean error : me (bias) = 0.06 1.h-1 (NS) relatively to weighted least-square estimates, n = 50). The precision of Bayesian prediction was comparable to that of the model independent which is used in routine practice and involves 9 measured levels over 30 h, (rmse = 1.35 1.h-1 (10.9%), n = 50). However, the routine method presented a significative bias (me = -0.81 1.h-1, n = 50).

Humans↗
PubMed1985

Free, glucuronide, and sulfate catecholamines in the rat: effect of hypoxia.

The formation and excretion of conjugated catecholamines (CA) was studied in conscious rats after sympathetic stimulation by hypoxia (5.5-6% O2, 4 h). Hypoxia induced a rapid and intense increase of free epinephrine (E, X 12) and norepinephrine (NE, X 6) but only a limited enhancement of free dopamine (DA, X 2). Sulfate conjugates of E and NE had kinetics similar to the free forms, while glucuronides were only moderately and lately altered. In contrast to free and sulfated DA, DA glucuronide, the major plasma conjugate, was decreased (-25%). This result suggests that DA glucuronide, unlike other CA conjugates, is not related to detoxication but might supply a CA precursor. Urinary conjugates badly reflected plasma conjugates. In normoxic controls, CA conjugates prevailed in the plasma, whereas the free amines prevailed in the urine. Hypoxia increased mainly the excretion of E and NE glucuronide but not of the free amines. Urinary DA, free or conjugated, was decreased (-25%), a result in keeping with plasma DA glucuronide only. The poor relations between plasma and urine catecholamines pinpoint the importance of the kidney in CA handling.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Studies on the central or peripheral origin of free and sulfated 3,4-dihydroxyphenylacetic acid in rat plasma.

The concentrations of free and sulfated 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in rat plasma to investigate their potential central or peripheral origin. Stimulation of central dopamine (DA) metabolism by a long-acting neuroleptic, pipotiazine (PPZ) selectively increased plasma levels of DOPAC sulfate whereas peripheral inhibition of monoamine oxidase by debrisoquin sulfate decreased free DOPAC levels only. These data suggest that the two forms of plasma DOPAC (free and sulfate) may have independent topographic origins. Peripheral DA pools seem to be the most likely sources for plasma free DOPAC whereas central dopaminergic neurons mainly contribute to plasma sulfated DOPAC. Our findings thus demonstrate that plasma DOPAC sulfate may be a useful indicator for central DA function in rat. Although further experiments are necessary to extrapolate our findings from rat to man, arguments are given indicating that measurements of plasma DOPAC sulfate might be of interest in human pathological and pharmacological investigations.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Methotrexate-vindesine association in the treatment of head and neck cancer influence of vindesine on methotrexate's pharmacokinetic behavior.

Determination of methotrexate (MTX) kinetics after an IV bolus (50 mg/m2) allows prediction of the steady-state plasma level of this drug during a constant infusion. This prediction allows high-dose MTX (HD-MTX) therapy without major toxicity. Patients with head and neck carcinoma received HD-MTX and vindesine (VDS) infusions concomitantly. The therapeutic survey of these patients showed that the predicted plasma level of MTX was not achieved in the presence of VDS. Moreover, the computed dose of MTX had to be increased by a larger amount if the MTX plasma clearance after the identification IV push was low (less than 9 l/h). In the presence of VDS, the creatinine clearance is lower than when MTX is infused alone, and MTX renal elimination is identical (MTX or MTX + VDS infusions). Thus it seems that the decrease of the MTX plasma level during MTX-VDS infusion could be due to an increase of cellular incorporation.

Adult↗