Biomedical subjects

F Fauvelle

Publications and source records attributed to F Fauvelle.

At least 37 records · Page 2Linked to original sources

PubMed1996

Synthetic pyridopurines derived from food pyrolysis products: intercalation, interactions with membranes, cyclodextrin complexation, and biological mitogenic properties.

Crucial conditions for the pharmacological use of active compounds are their ability to cross the biological barriers and reach their intracellular target. In the case of two antiviral pyridopurine derivatives, 1 and 2, this included essentially the membranes and the nucleic acids. Thus the interactions of 1 and 2 with model membranes and oligonucleotides were studied using NMR spectroscopy. It was found that these hydrophobic molecules can be incorporated into the model membranes at the terminal methyl group level, inducing dynamic perturbations in the bilayer. In the presence of the synthetic oligonucleotide ACATGT, both molecules can intercalate aspecifically in AT and GC systems. Inclusion complexes of 1 and 2 beta-cyclodextrins with a 1:1 stoichiometry, were also prepared. This led to to propose two galenic forms 1 and 2, i.e. included in phospholipid vesicles in the form of a beta-cyclodextrin complex

Amines↗

PubMed1996

Imidazo[1,2-a]pyridine derivatives as antiviral agents: biological assays and NMR study of their interactions with membranes and oligonucleotides.

Three potentially antiviral imidazo[1,2-a]pyridine derivatives of increasing hydrophilicity were tested in their interactions with model membranes and synthetic oligonucleotides. It was shown that the most hydrophobic derivative [1], located in the depth of the bilayer only induces minor membrane damages. The molecule [2], only poorly hydrophobic, integrates also the bilayer in the medium part of the chains while the most hydrophilic [3] exhibits fluidizing and slightly detergent properties. In the presence of synthetic oligonucleotide ACATGT no intercallation of the three derivatives was evidenced. By considering their antiviral activity in the absence of evident mitogenic properties, another mechanism of action was proposed.

Antiviral Agents↗

PubMed1995

Measurement of 4-hydroxycyclophosphamide in serum by reversed-phase high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method was developed for the measurement of 4-hydroxycyclophosphamide (4-OH-CP) in human serum, since no such assay has been described to date. In the present procedure, the serum sample was treated with semicarbazide at pH 7.4 to derivatize the 4-OH-CP to its aldophosphamide semicarbazone form. Derivatization was performed at 60 degrees C for 60 min and the product was extracted with ethyl acetate-chloroform (75:25, v/v). The derivatives formed were chromatographed on a C8 reversed-phase column with a mobile phase of 0.025 M phosphate buffer-acetonitrile (18:82, v/v) and a detection wavelength of 230 nm. The limit of detection of the assay was 0.025 mg/l for 1 ml of serum with a signal-to-noise ratio of 2. The between-assay coefficients of variation at concentrations of 0.2 and 0.4 mg/l were 7.7 and 7.0% respectively. The simplicity and specificity of this method make it directly applicable to clinical studies on 4-OH-CP pharmacokinetics.

Chromatography, High Pressure Liquid↗

PubMed1995

[NMR study of membrane incorporation of cysteamine].

The incorporation of the cysteamine molecule in small unilamellar vesicles was studies using proton NMR technics. A linear inclusion of the radioprotective molecule was firstly observed by increasing the Cysteamine/phospholipid molar ratios, followed by a saturation for the highest ratios. Such results may be adapted to a new galenic form study.

Cysteamine↗

PubMed1995

[Interaction between 4-hydroxynonenane with membrane system. 1H, 31P, 2H NMR study].

The interactions between membranes and 4-hydroxynonenane (HNE)-a natural product of polyinsatured fatty acids peroxidation-were investigated by NMR spectroscopies. This molecule is located in the intermediate part of the bilayer. The presence of the HNE induces an increase of the fluidity in the deep part of the membrane, while a rigidification of the superficial part is found.

Aldehydes↗

PubMed1994

Pharmacokinetics of cyclophosphamide in patients with systemic necrotizing angiitis.

Cyclophosphamide pharmacokinetics were investigated following administration to patients with systemic necrotizing angiitis. Ten patients (eight women and two men) received cyclophosphamide as a 1-h-rate-constant intravenous infusion at doses ranging from 600 to 1200 mg. All patients received concomitant oral prednisone (1 mg/kg/d). Blood samples were collected at the end of drug infusion and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h later. Serum cyclophosphamide concentrations were assayed by high pressure liquid chromatography. The peak serum cyclophosphamide levels ranged from 15.7 to 29.4 mg/L. The mean cyclophosphamide elimination half-life was 6.2 +/- 1.3 h (mean +/- SD). The mean apparent volume of distribution and mean total plasma clearance were, respectively, 0.75 +/- 0.22 L/kg (mean +/- SD) and 83 +/- 22 mL/min (mean +/- SD). These results obtained in systemic vasculitic diseases were consistent with those observed in other studies with cancer patients receiving comparable doses of cyclophosphamide.

Adult↗

PubMed1994

Fever and associated changes in glomerular filtration rate erase anticipated diurnal variations in aminoglycoside pharmacokinetics.

Netilmicin (4.5 mg/kg of lean body weight) was administered intravenously once every 24 h at 10 a.m. to 23 patients (group I) and at 10 p.m. to 20 patients (group II) with severe infection. No significant differences (P > 0.05) in peak and trough concentrations in serum were found between groups I and II (peak, 12.9 +/- 3.7 versus 12.8 +/- 4.4 mg/liter, respectively; trough, 0.7 +/- 0.6 versus 0.8 +/- 0.6 mg/liter, respectively [mean +/- standard deviation]). Pharmacokinetic parameters (half-life [5.0 +/- 2.2 versus 4.9 +/- 1.8 h], volume of distribution [0.32 +/- 0.04 versus 0.35 +/- 0.06 liter/kg], and total clearance [0.920 +/- 0.417 versus 1.015 +/- 0.546 ml/min/kg]) were similar in the two groups and not influenced by the time of administration. These data suggest that, in the once-daily schedule, 10 a.m. or 10 p.m. administration had no influence on netilmicin levels in serum and pharmacokinetic parameters in these ill febrile patients.

Adult↗

PubMed1994

Pharmacokinetics of ceftriaxone during plasma exchange in polyarteritis nodosa patients.

Plasma exchange (PE) is currently being used to treat a variety of disorders involving immune complexes, such as polyarteritis nodosa. This procedure removes endogenous toxic components that accumulate in patients with this disease, but it also removes drugs. Plasma-protein binding and the volume of distribution (V) are two kinetic parameters which strongly affect the efficiency of drug removal by PE. Drugs that are highly bound to plasma proteins and have a low V may show a marked decrease in plasma levels as a result of PE. Because ceftriaxone exhibits saturable plasma-protein binding, which influences its pharmacokinetic parameters, particularly its V, we evaluated its removal during PE therapy in this nonrandomized crossover study. Twelve polyarteritis nodosa patients undergoing PE were studied. Each patient was given ceftriaxone intravenously in doses of 1 and 3 g on days 4 and 11, respectively, immediately before (n = six patients; group I) and 6 h before (n = six patients; group II) PE. Plasma was assayed for ceftriaxone by high-pressure liquid chromatography. The mean amounts eliminated +/- standard deviations were 230.8 +/- 38.5 mg (1 g) and 750.0 +/- 168.5 mg (3 g) for group I and 161.0 +/- 66.0 mg (1 g) and 347.0 +/- 121.0 mg (3 g) for group II. The drug fractions eliminated by PE were 23.0% +/- 3.9% (1-g dose) and 24.9% +/- 5.6% (3-g dose) for group I (P > 0.05), and 16.6% +/- 5.9% (1-g dose) and 11.5% +/- 4.0% (3-g dose) for group II (P < 0.05). These results showed that the drug fraction eliminated decreased when V increased only when the distribution phase of ceftriaxone had been completed (group II). These findings suggest that PE may influence ceftriaxone disposition and that it would be better to administer the drug after PE to assure its therapeutic efficacy.

Adult↗

PubMed1994

[Demonstration of molecular combinations of alpha cyclodextrin (ACD) with dioctanoyl glycerol].

The molecular association of dioctanoyl glycerol (DOG) with the natural alpha cyclodextrin molecule (ACD) was studied using small unilamellar vesicles (SUV) by proton and 13C NMR. While no classic inclusion complex was found, a molecular association exists, leading to the formation of an insoluble precipitate. The possibility of a polar head group implication is discussed about the dimyristoyl phosphatidyl choline model.

Cyclodextrins↗

PubMed1994

Naphtyl methyl imidazoline (NMI) membranes interactions: NMR study and evaluation of possible radioprotective consequences.

The interactions of the radioprotective molecule Naphtyl methyl imidazoline (NMI) with membranes have been studied using biophysical and biochemical methods. 1H, 2H and 31P-NMR methods showed a strong interaction with the deep part of the layer of model membranes inducing the formation of a new membrane compartment. These properties are not involved in the radioprotection effect of NMI which is more probably due to its vasoconstrictive properties.

Humans↗

PubMed1993

Pharmacokinetics and clinical study of cefotetan in bile: prophylactic use in biliary tract surgery.

The excretion of cefotetan, a 7 alpha-methoxy-cephalosporin, was studied in 27 patients undergoing biliary surgery. Pharmacokinetic parameters were determined after a single intravenous bolus dose of 1 g (10 patients) or 2 g (17 patients). Rapidly excreted in bile, cefotetan concentrations were considerably higher in bile [range: 92-2,594 mg.l-1 (1 g); 35-4,610 mg.l-1 (2 g)] than in plasma despite the presence of gall stones. Bile bactericidal activities against Staphylococcus aureus (MIC 8 mg.l-1) and Bacteroides fragilis (MIC 2 mg.l-1) correlated well with gall bladder cefotetan levels [r = 0.888 (1 g); r = 0.971 (2 g)]. No cefotetan was detected in the bile of 3 patients with nonfunctioning gall bladders. One other patient with very low activity and these three aside, the inhibitory quotients (cefotetan concentration/MIC) were > 4 for both doses against both bacteria.

Adult↗

PubMed1993

Treatment of polyarteritis nodosa related to hepatitis B virus with short term steroid therapy associated with antiviral agents and plasma exchanges. A prospective trial in 33 patients.

OBJECTIVE: To test the effectiveness and tolerance of antiviral agents associated with short term immunosuppression in the treatment of polyarteritis nodosa (PAN) related to hepatitis B virus (HBV). METHODS: We conducted a prospective, nonblinded, multicenter trial in which patients with multisystemic PAN related to HBV were included. Every patient initially underwent a short term (2 weeks) treatment with prednisone and then received vidarabine (Vira A) and plasma exchanges. The end point of the study was control of the disease (recovery or remission) or death. RESULTS: Thirty-three patients were included. Every patient had histopathologic or arteriographic evidence of vasculitis and was infected with actively replicating HBV. Disease activity during the first 6 months was controlled in 26 patients (78.8%). Among the 25 patients still alive at the end of the study, 24 (72.7%) had completely recovered with no clinical or laboratory evidence of systemic vasculitis after at least 18 months without treatment. Eight patients died during the study period; 3 of treatment failure, usually early in the course of the disease. One patient died of fulminant hepatitis 3 months after the entry in the study at time of seroconversion. The survival curve showed that at 7 years, 76% of the patients were alive. HBeAg/anti-HBeAb seroconversion was observed in 12 patients (36.3%) after one Vira A cycle. When a 2nd cycle of Vira A or alpha interferon was prescribed, HBeAg/anti-HBeAg seroconversion occurred in 15 patients (45.4%). Two other patients who underwent a 2nd cycle of Vira A administration, had lost HBeAg and no longer expressed serological evidence of replication as assessed by HBV DNA spot hybridization. At the end of the study, 17 (51.5%) no longer expressed serological evidence of HBV replication. This treatment was effective and only minor side effects were noted. CONCLUSIONS: We conclude that this new therapeutic approach to PAN related to HBV effectively controlled systemic vasculitis and was associated with a higher number of recoveries from chronic HBV infections. The development of new antiviral agents, such as interferon alpha 2b, allows us to hope that antiviral therapy will have a role to play as a first line treatment regimen of virus induced vasculitis.

Adult↗

PubMed1992

Interaction of the malonyldialdehyde molecule with membranes. A differential scanning calorimetry, 1H-, 31P-NMR and ESR study.

The membrane interactions of malonyldialdehyde (MDA), natural product of polyunsaturated fatty acids peroxidation were investigated by differential scanning calorimetry, and ESR or NMR spectroscopy. This component is located in the superficial part of the bilayer, where it increases the local fluidity. High concentrations of MDA induce major membrane damage. Similar consequences of MDA-membrane interactions were observed on erythrocyte ghosts.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1992

Pharmacokinetics of vidarabine in the treatment of polyarteritis nodosa.

The pharmacokinetics of vidarabine were studied in 8 patients with polyarteritis nodosa related to hepatitis B virus infection. The drug was administered by continuous infusion for three weeks at doses of 15 (1 week) and 7.5 (2 weeks) mg/kg per day, during which time 15 plasma exchanges were performed. Plasma was assayed for vidarabine and its principal metabolite, hypoxanthine arabinoside by high pressure liquid chromatography. Vidarabine was not detected in the plasma of any patients. Hypoxanthine arabinoside levels were used to evaluate vidarabine kinetics. The serum levels of hypoxanthine arabinoside ranged from 3.6 to 21.5 mg/l. The mean elimination half-life (+/- SD) was 3.0 +/- 1.7 h. The plasma clearance (mean +/- SD) was 195 +/- 270 ml/min when the dose was 7.5 mg/kg per day and 66.3 +/- 47 ml/min for a 15 mg/kg per day/dose (NS). Except for the elimination half-life, these results were not fully consistent with those observed in other studies. The influence of multiple plasma exchanges on vidarabine kinetics is limited and dosage adjustment is not required based on the continuous infusion of vidarabine.

Humans↗

PubMed1992

Pharmacokinetics of glafenine and glafenic acid in patients with cirrhosis, compared to healthy volunteers.

Pharmacokinetic parameters were evaluated in 12 patients with alcoholic cirrhosis and 12 healthy volunteers after a single 400 mg oral dose of glafenine. Glafenine (G) and its major active metabolite glafenic acid (GA) were measured at regular intervals using a specific high performance liquid chromatographic method. Glafenine absorption was significantly delayed in cirrhotic patients (CP) (Tmax = 2.8 +/- 1.3 hvs 1.5 +/- 0.4 h, p less than 0.01) and was dramatically reduced in 3 patients. The large hepatic 'first pass' effect observed in healthy volunteers was markedly reduced in CP (ratio Cmax GA/Cmax G = 3.6 +/- 2.9 vs 18.9 +/- 9.8, p less than 0.001; ratio areas under the curves AUC GA/AUC G = 2.3 +/- 2.3 vs 18.2 +/- 11.2, p less than 0.001). The elimination half-life of G was prolonged in the CP (13.0 +/- 13.1 h vs 1.5 +/- 0.5 h, p less than 0.01). In CP, GA elimination half-life was increased (12.0 +/- 13.4 h vs 4.3 +/- 1.3 h, NS) but the difference did not reach statistical significance because of large variability. The significant rise of G plasma concentrations (Cmax = 2.2 +/- 2.1 mg/L vs 0.7 +/- 0.2 mg/L, p less than 0.05) and its longer half-life would lead to an accumulation if the usual dosage regimen was prescribed for CP and could result in nephrotoxicity. On the other hand, lower dosage would be ineffective because only GA is active and nephrotoxic. Hence, G should be given with great caution to CP.

Administration, Oral↗

PubMed1991

Zidovudine removal during plasma exchange.

Pharmacokinetics of zidovudine (azidothymidine, AZT) were investigated after oral administration (300 mg every 8 hours) in a human immunodeficiency virus seropositive patient who was also treated with plasma exchange (60 ml/kg). Plasma AZT concentrations were measured using high performance liquid chromatography assay. Plasma exchange clearances reached 1-3.8% of the total clearance. The fraction of AZT removed from separated plasma accounted for only 1% of the administered dose. The contribution of plasma exchange to the elimination of AZT appears to be negligible. Solely on the basis of AZT pharmacokinetic data, no particular dose adjustment appears to be necessary in patients treated with multiple plasma exchanges.

Adult↗

PubMed1988

Effective high-performance liquid chromatographic determination of glafenine in plasma: pharmacokinetic application.

A high-performance liquid chromatographic method for an effective determination of glafenine and its main metabolite, glafenic acid, is described. The assay involves separate extraction procedures for glafenine and for its metabolite, but the same internal standard (floctafenine) and the same chromatographic conditions (including a 5-micron C8 column, a quaternary solvent mixture of water-acetonitrile-diethylamine-acetic acid and an ultraviolet detector set at 360 nm). For 1 ml of plasma, the detection limit is 0.05 mg/l for glafenine and 0.25 mg/l for glafenic acid. Compared with previously described techniques, this assay uses a very low glafenine linearity range, which allows the true pharmacokinetics of this drug to be described for the first time.

Chromatography, High Pressure Liquid↗

PubMed1988

Pharmacokinetics of paracetamol, diclofenac and vidarabine during plasma exchange.

In order to establish guidelines for prescribing drugs in patients treated with plasma exchange (PE), we studied the pharmacokinetics of paracetamol (5 patients), diclofenac (4 patients) and vidarabine (3 patients) during one or several PE. Results were compared with those obtained without PE. Diclofenac and paracetamol were chosen because they presented different volume distribution and protein binding characteristics. Vidarabine was studied because we use it for the treatment of patients with polyarteritis nodosa related to hepatitis B virus. Diclofenac (100 mg) and paracetamol (1000 mg) were given 1 hour before PE. Samples were obtained 60 and 30 min before PE, every 15 min during PE and hourly for 2 hours after the end of PE. Vidarabine was given in continuous infusion, 15 mg/kg/d during the first week of treatment and 7.5 mg/kg/d during subsequent weeks. Samples were obtained before PE, 3 times during PE and every 30 min for 4 hours after the end of PE. Paracetamol, diclofenac, vidarabine and hypoxanthine arabinoside were assayed by high performance liquid chromatography. During each PE 60 ml/kg were removed and replaced by albumin. We found that 17% of diclofenac, 4.3% of paracetamol and 4.9% of vidarabine were removed during each session. Plasmapheresis clearance was 51% of plasma clearance for diclofenac, 15% for paracetamol and 10% for vidarabine. Drugs which are mainly removed during PE are those which are bound to proteins with a small distribution volume. Those drugs, such as diclofenac, must be administered after the end of each PE session. Drugs which present a large distribution volume and low protein binding can be given before the session. Vidarabine can be administered during PE without loss of effectiveness due to drug removal.

Acetaminophen↗