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F Fauvelle

Publications and source records attributed to F Fauvelle.

45 records · Page 3Linked to original sources

Improved determination of sulpiride in plasma by ion-pair liquid chromatography with fluorescence detection.

A specific and sensitive high-performance liquid chromatographic method for the measurement of sulpiride in plasma is described. The internal standard used was veralipride, a structurally related substituted benzamide. A fluorescence detector with maximum excitation at 300 nm and maximum emission at 365 nm was used for quantitation. After an alkaline extraction procedure, the benzamides were separated on a 5-micron ODS column using a large organic counter ion in the mobile phase. The detector response was linear from 10 to 1000 ng/ml and the detection limit was 10 ng/ml, which is sensitive enough for pharmacokinetic studies. The suitability of the method for the analysis of biological samples was tested by studying the variation with time of plasma concentrations of sulpiride in normal human volunteers after a single therapeutic 200-mg oral dose of three different formulations of sulpiride.

Chromatography, High Pressure Liquid↗

Diclofenac, paracetamol, and vidarabine removal during plasma exchange in polyarteritis nodosa patients.

Since plasma exchange (PE) represents a major treatment for patients suffering from systemic diseases, its influence on the kinetics of three drugs was investigated: vidarabine, used in patients with polyarteritis nodosa associated with hepatitis B virus (eight subjects), and diclofenac and paracetamol for investigative purposes (five subjects). This study confirmed that vidarabine is so rapidly deaminated to form hypoxanthine arabinoside (Hx-Ara) that no detectable concentrations were measured. Hx-Ara levels were used to evaluate vidarabine kinetics; 19.5 +/- 14.6 mg of Hx-Ara were removed by one PE during the first week of treatment (15 mg kg-1 d-1, continuous infusion) and 7.8 +/- 10.2 mg were eliminated by one PE during the second week of treatment (7.5 mg kg-1 d-1, continuous infusion). Based on the vidarabine intake per hour and the resulting quantity of Hx-Ara removed per hour, PE recovery was quite important (ca. 30 per cent), during both the first and second weeks of continuous infusion. Data were subject to large interindividual variability. However, these results do not favor vidarabine dosage supplementation in this indication because the duration of PE is less than 8 per cent of a daily administration period. For paracetamol (1 g, single oral dose) and diclofenac (100 mg, single oral dose), the fractions of drug removed during PE effected within 2 h of drug intake, were respectively 5.0 +/- 3.1 per cent and 13.6 +/- 9.5 per cent, while plasmapheretic clearance reached, respectively, 13.0 +/- 10.7 per cent of the systemic clearance for paracetamol and 23.0 +/- 1.0 per cent for diclofenac.

Acetaminophen↗

Pharmacokinetics of cyclophosphamide (CP) and 4-OH-CP/aldophosphamide in systemic vasculitis.

Cyclophosphamide given in association with corticosteroids has markedly improved the prognosis of systemic vasculitis. Little information has been reported on cyclophosphamide pharmacokinetics in these diseases and data evaluating its metabolite, 4-hydroxycyclophosphamide/aldophosphamide, pharmacokinetics and concentrations are lacking. Cyclophosphamide was administered as a 1-h intravenous infusion every 3 weeks for six cycles to ten vasculitis patients. Serum cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide concentrations were assayed on the first cycle of the treatment by reversed-phase high-pressure liquid chromatography with ultraviolet detection. The mean (+/- SD) 4-hydroxycyclophosphamide/aldophosphamide and cyclophosphamide areas under the serum concentration-time curves were, respectively, 1.86 +/- 1.12 and 154.1 +/- 62.7 mg/L x h with a ratio of 1.30 +/- 0.76%. The mean maximum serum 4-hydroxycyclophosphamide/aldophosphamide was reached 2.3 h after cyclophosphamide administration. The mean (+/- SD) cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide half-lives were, respectively, 5.5 +/- 3.1 and 7.6 +/- 2.3 h. The results are consistent with those obtained for cancer patients, in spite of a wide interpatient variability of concentrations and pharmacokinetic parameters.

Adult↗

Clinical pharmacokinetics during plasma exchange.

Drug removal during plasma exchange (PE) is a complex phenomenon that is defined by the molecule pharmacokinetic characteristics. Plasma-protein binding and the volume of distribution (Vd) are two kinetic parameters that strongly affect the efficiency of drug removal by PE. The effect of PE on drug kinetics has been specifically studied with antivirals, cardiotonic agents, antibiotics, corticosteroids, antalgics, anti-epileptic agents and non-steroidal anti-inflammatory drugs. This effect can be evaluated using different parameters: extracorporeal clearance, half-life, amount eliminated, and fraction of the drug removed. The estimated fraction eliminated (Fe) from the body by PE is the best parameter to evaluate the effectiveness of the exchange procedure; it can account for 0.5-30 per cent. Results reported in the literature showed that PE most influences drugs with a low Vd, regardless of the extent of protein binding. We established that, during PE, there is a linear relationship between Fe and the fraction of the drug in extracellular fluids. The fraction eliminated during PE is approximately one-seventh of the fraction of the drug in extracellular fluids. We propose to use this extracellular fraction as a predictive index: when < 20, extraction is low; the amount eliminated becomes consequential only when the index > 20. Dosage supplementation may be needed to maintain an adequate drug concentration in the body. Practically, for drugs with a low Vd (< 0.3 l/kg), it seems necessary to adjust the dosage.

Algorithms↗

Is uranyl scavenger hexakis(3,6-anhydro) tetrakis(2A,B,D,E-O-octyl) cyclomaltohexaose (OCT) relevant with biosystems?

Hexakis(3,6-anhydro)tetrakis(2A,B,D,E-O-octyl) cyclomatohexaose (OCT) has been recently shown as a powerful cryptant for lead, mercury, and especially for uranyl. As previous results have been obtained in an organic solvent (methanol), a similar evaluation of OCT complex formation was achieved in aqueous medium and in the presence of membrane-mimicking systems such as phospholipid vesicles, liposomes and micelles. It was found that OCT, while completely insoluble in water, forms solid gel structures when in equimolar mixtures of water and methanol. Moreover, OCT exhibits detergent properties. Finally, OCT was successfully introduced in detergent solutions while keeping. Uranyl complexing properties. Possible applications of such models were also discussed.

Chelating Agents↗

1H-NMR study of heavy metals complexation with hexakis(3,6-anhydro) tetrakis(2A,B,D,E-O-octyl) cyclomaltohexaose (OCT).

The selection of the cations bound by hexakis (3,6-anhydro) tetrakis (2A,B,D,E-O-octyl) cyclomatohexaose (OCT) was performed by thin layer chromatography. The three cations selected, UO(2)2+, Pb2+ and Hg2+ were then studied by 1H-NMR. A 2:1 OCT/cation stoichiometry was identified in the cases of UO(2)2+ and Pb2+. While UO(2)2+ binding (logK around 6) followed a fast exchange kinetics, a slow or intermediate complexation was found with Pb2+ (logK = 5.6) and Pb2+, respectively. In the latter case, the poor solubility of Hg2+ precluded to propose neither a stoichiometry nor an estimation of the affinity constant.

Chelating Agents↗

[Extraction of drugs in plasma exchange].

Plasma exchange has been proposed for treating diseases mediated by circulating immune complexes. Removal of drugs during plasma exchange is a complex function of pharmacokinetic characteristics and specifications of the plasma exchange procedure: the time of plasma exchange, the filtered volume of plasma, the number of procedure. The effect of plasma exchange on the kinetics of drugs can be evaluated by different parameters: amount eliminated, extracorporeal clearance, fractional drug removal, extracorporeal elimination rate constant. Knowledge of the impact of plasma on the elimination of drugs is essential to the design of the dosage regimen in patients treated with plasma exchange. The fraction of the estimated amount in body removed by plasma exchange is the best parameter to evaluate the effectiveness of the exchange procedure, but it is necessary to know the proportion of body pool of drug at the start of the plasma exchange. Drug recovery by each exchange may account for 0.5%-30% of the dose. Controlled studies are needed to quantify the effects of plasma exchange on drug therapy. Dosage adjustment is sometimes required.

Humans↗