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Biomedical subjects

O Lafont

Publications and source records attributed to O Lafont.

At least 19 recordsLinked to original sources
PubMed2001

Effects of encapsulation of primidone on its oxidative metabolism in rats.

The aim of this study was to evaluate the influence of primidone (PRM) nanoencapsulation on its metabolism. Suspensions of PRM powder and PRM-loaded poly-epsilon-caprolactone nanocapsules were administered orally in the same way to rats. Primidone-loaded poly-epsilon-caprolactone nanocapsules were prepared according to the interfacial deposition technique. Free PRM suspensions were obtained by addition of PRM powder to a suspension of 0.212% carboxymethylcellulose CMC 12H in water. The dose was 20 mg/kg, n = 6, for each experiment. Urinary and faecal levels of PRM and of its three major metabolites, phenylethylmalonamide (PEMA), phenobarbital (PB), and p-hydroxyphenobarbital (p-HO-PB), were determined. Concentrations were evaluated by high-performance liquid chromatography (HPLC) according to a validated analytical method. After PRM nanocapsule administration, non-metabolised PRM urinary levels were increased compared to those observed after administration of a suspension of primidone powder (43.7+/-8.8% after PRM-loaded nanocapsule and 37.7+/-8.1% after free PRM administration). For phenylethylmalonamide, no difference was observed in urinary excretion in the two cases. For two of the oxidised metabolites, PB and p-HO-PB, excretion was delayed and shortened. The amount of these oxidised metabolites was lowered from 0.95% after free PRM administration to 0.25% after PRM-loaded nanocapsule administration. No difference was noted in non-metabolised primidone excretion in faeces. These results suggest that primidone-loaded nanocapsules could be used as a vehicle for oral primidone administration in order to minimise the phenobarbital metabolic pathway.

Animals↗
PubMed2000

University education of medicinal chemists: comparison of eight countries.

Medicinal chemists are mainly taught in faculties or schools of pharmacy and are available for employment. Yet major pharmaceutical research companies seek organic chemists, rather than medicinal chemists, for new drug discovery. This apparent contradiction led the Medicinal Chemistry Section of IUPAC to send a questionnaire regarding postgraduate academic education for medicinal chemists to the faculties or schools of pharmacy in eight countries, namely, France, Germany, Italy, Japan, Spain, Switzerland, UK and USA. The questionnaire aimed to elicit information about postgraduate medicinal chemistry students, their courses and training, and the occupations taken up after graduation. The replies representing 109 medicinal chemistry departments or sections have been analysed and the results are presented to provide a data base on modern medicinal chemistry curricula for comparative purposes. The information should help guide discussion of the optimum paths to be followed by students in preparation for their careers. The evidence suggests that academic training of medicinal chemists equips them to enter a wide range of occupations, many of which are in industry.

Chemistry, Organic↗
PubMed2000

Competition between the beta-hydroxylation of a primary and a tertiary carbon atom in rats.

In order to study the effect of steric hindrance on competition between two kinds of beta-hydroxylation, a compound bearing on a pyrimidinetrione nucleus both a branched side chain with a tertiary carbon atom in position beta (isobutyl group) and a linear side chain (ethyl group), was selected and administered to rats. Urine and faeces were collected and extracted. Hydroxymetabolites and their derivatives were isolated and then identified. The beta-hydroxylation of the linear chain was more important than the beta-hydroxylation of the branched chain. Steric hindrance plays a decisive role in this regioselectivity.

Animals↗
PubMed2000

[Aspirin throughout the ages: a historical review].

Even at the beginning of the next millennium, aspirin will still offer surprises. Its relatively young pharmacological history compares with the early use of salicylate-containing plants since antiquity. The Assyrians and the Egyptians were aware of the analgesic effects of a decoction of myrtle or willow leaves for joint pains. Hippocrates recommended chewing willow leaves for analgesia in childbirth and the Reverend Edward Stones is acknowledged as the first person to scientifically define the beneficial antipyretic effects of willow bark. At the beginning of the 19th century salicin was extracted from willow bark and purified. Although a French chemist, Charles Gerhardt, was the first to synthesize aspirin in a crude form, the compound was ignored, and later studied by Felix Hoffmann. He reportedly tested the rediscovered agent on himself and on his father, who suffered from chronic arthritis--a legend was born and Bayer Laboratories rose to the heights of the pharmacological world. First used for its potent analgesic, antipyretic and anti-inflammatory properties, aspirin was successfully used as an antithrombotic agent. Sir John Vane elucidated aspirin's active mechanism as an inhibitor of prostaglandin synthetase and received the Nobel Price in Medicine for this work in 1982. Two isoform of cyclooxygenase (COX-1 and COX-2) have now been identified, each possessing similar activities, but differing in characteristic tissue expression. The cox enzyme is now a target of drug interventions against the inflammatory process. After two centuries of evaluation, aspirin remains topical, and new therapeutic indications are increasingly being studied.

Adult↗
PubMed2000

[Some steps of the history of Pharmacy in Rouen].

The community of apothecaries was created in Rouen, in 1508, and its statutes were completed in 1588. The Le Chandelier family was a good example of a dynasty of apothecaries. Precise information on the way of life of XVIIth century apothecaries was given by Jacob Congnard's post mortem inventory. This document revealed also the part played by the apothecaries in foreign trade. The contribution to science was represented by Nicolas Lemery and Francois-Antoine-Henri Descroizilles. After the modifications of the rules by the law of Germinal an XI, the Preparatory School of Medicine and Pharmacy was created in 1841, but it became a faculty, only in 1966.

France↗
PubMed2000

[Wholesale dealers and apothecaries in Rouen].

Wholesale dealers are merchants who sell only great amounts of drugs. Since the XVIth century, the conditions under which they practiced were governed by apothecaries' statutes. The control of drugs, which was performed by apothecaries, was often contested by wholesale dealers. After many proceedings, the court decided in favor of apothecaries.

Commerce↗
PubMed1999

Primidone-loaded poly-epsilon-caprolactone nanocapsules: incorporation efficiency and in vitro release profiles.

This paper describes the preparation of primidone-loaded poly-epsilon-caprolactone nanocapsules according to the interfacial deposition technique. The colloidal suspension obtained showed a monomodal size distribution with a mean diameter ranging from 308 to 352 nm. By adjusting the process parameters, the encapsulation efficiency was about 74% with good reproducibility. Primidone release from the nanocapsules was found to be slower as compared to the oily control solution despite an important burst-effect. The release profile was not influenced by the pH of the release medium.

Caproates↗
PubMed1999

[The 1791 project of rules for pharmacy: an attempt, in Rouen, to find an alternative to apothecaries' communities].

In 1791, the apothecaries' communities were suppressed, but two weeks later the ancients rules were restored. Nevertheless this situation was provisional and it was time to think of new regulations. The apothecaries from Rouen redacted a project inspired by both the 1508 regulations and the Royal 1777 declaration creating the College of Pharmacy in Paris. This project does not seem to have received any application. The statutes of the free society of pharmacists of Rouen created in 1802, did not refer to this project.

France↗
PubMed1999

[Eau de mille-fleurs which made Kings' cat dance].

King Louis XV had a cat and some of his courtiers forced it to dance using eau de mille-fleurs (thousand flowers water). This name was given both to cow urine and to the distilled water obtained from cow dung. In this case, the medicine used was George Bate's eau de mille-fleurs, which contained alcohol.

Animals↗
PubMed1998

Simultaneous determination of primidone and its three major metabolites in rat urine by high-performance liquid chromatography using solid-phase extraction.

A new high-performance liquid chromatographic method for simultaneous determination of primidone (PRM) and of its three major metabolites, phenobarbital (PB), p-hydroxyphenobarbital (p-HO-PB) and phenylethylmalonamide (PEMA), in rat urine, was developed. After acid hydrolysis, these compounds were extracted from urine by means of a Bond Elut Certify LRC column with good clean-up. The extracts were chromatographed on a C18 reversed-phase column using isocratic elution at 40 degrees C, with UV detection at 227 nm. The limit of detection was 0.5 mg/ml for the four compounds. Good linearity (r2>0.99) was observed within the calibration ranges studied: 37.4-299.3 microg/ml for PRM, 26.4-211.2 microg/ml for PB, 12.5-100.2 microg/ml for p-HO-PB and 12.1-97.0 microg/ml for PEMA. Repeatability was in the range 3.1-6.8%. This method constitutes a useful tool for studies on the influence of various parameters on primidone metabolism.

Animals↗
PubMed1998

Entrapment efficiency and initial release of phenylbutazone from nanocapsules prepared from different polyesters.

Several formulations of poly(epsilon-caprolactone) (PCL), poly(lactic acid) (PLA), and poly(lactic-co-glycolic acid) (PLGA) nanocapsules containing phenylbutazone were prepared according to the interfacial deposition technique. These formulations differed in the type of polymer used to form the shell of the nanocapsules. Analysis of particle size distribution and encapsulation efficiency of the nanocapsules revealed that the type and molecular weight of polyester used were the main factors influencing these properties. PLA had the highest encapsulation efficiency with the best reproducibility. From in vitro release studies, a small amount of drug release was observed at pH 7.4. However, in the gastric medium, an important burst effect occurred and was highest with the PLGAs and lowest with PCL, suggesting that drug release from these systems is affected by the type of polymer and the environmental conditions. The two formulations of phenylbutazone-loaded nanocapsules should be evaluated based on PCL and PLA in vivo in order to determine to what extent they are able to reduce the local side effects of this drug.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Determination of pyrazinamide and its main metabolites in rat urine by high-performance liquid chromatography.

A new high-performance liquid chromatograhic procedure for simultaneous determination of pyrazinamide (PZA) and its three metabolites 5-hydroxypyrazinamide (5-OH-PZA), pyrazinoic acid (PA), and 5-hydroxypyrazinoic acid (5-OH-PA), in rat urine was developed. 5-OH-PZA and 5-OH-PA standards were obtained by enzymatic synthesis (xanthine oxidase) and checked by HPLC and GC-MS. Chromatographic separation was achieved in 0.01 M KH2PO4 (pH 5.2), circulating at 0.9 ml/min, on a C18 silica column, at 22 degrees C. The limits of detection were 300 microg/l for PZA, 125 microg/l for PA, 90 microg/l for 5-OH-PZA and 70 microg/l for 5-OH-PA. Good linearity (r2>0.99) was observed within the calibration ranges studied: 0.375-7.50 mg/l for PZA, 0.416-3.33 mg/l for PA, 0.830-6.64 mg/l for 5-OH-PZA and 2.83-22.6 mg/l for 5-OHPA. Accuracy was always lower than +/- 10.8%. Precision was in the range 0.33-5.7%. The method will constitute a useful tool for studies on the influence of drug interactions in tuberculosis treatment.

Animals↗
PubMed1997

[A short letter revealing the concerns of XVIIIth century apothecaries].

A letter from Demoret, Paris apothecary, to Le Chandelier, Rouen apothecary, evoked the defense of the interests of the profession, the practice of the profession and the family life of apothecaries of the XVIIIth Century. The important question of the examinations of hospital apothecaries, called "gagnants-maîtrises", and the question of soft drinks makers sailing syrups were treated. The trouble caused by the public display of theriaca, the illness of an assistant or the inspection by guards and physicians were described. Drug supply by colleagues from another town was pointed out. Finally the family life showed the hardness of the period and the way the sons of an apothecary were educated. The interest of this text is that it gives the opinion of an individual concerning general matters.

Antidotes↗
PubMed1997

[The Gallot affair, or the long history of drugs from the Flanders army].

After the war, for the Austrian succession, the drugs which had been prepared for the french army, operating in Flanders, were sold to a grocer from Rouen, Pierre Gallot. He tried during twenty years to sail these drugs, which were getting older and older. The apothecaries' community members made their best to avoid the dispensation of these faulty drugs by an unqualified person. These periods 1750, 1756-1758 and 1770-1771 were especially rich in incidents. Many documents allow to follow the evolution of the conflict. Finally the grocer was condamned.

Drug and Narcotic Control↗
PubMed1996

Phenobarbital metabolism by hepatocytes isolated from rat.

In order to test the validity of the use of hepatocytes as an alternative to studies of metabolism in live animals, phenobarbital (PB) was applied at 37 degrees C to isolated rat hepatocytes, which had been previously induced by PB. The metabolites were extracted by ethyl acetate, at various pH, and identified and evaluated by GC-MS. PB was not metabolized to p-hydroxyphenobarbital as is usually the case in living animals, but it was transformed into sulphoconjugated 2-phenyl-gamma-butyrolactone. This pathway, beta-hydroxylation of the ethyl side chain followed by lactonization, previously described as a secondary metabolic pathway occurring during intoxications, was here the only observed biodegradation. These results show that it is not possible to use hepatocytes as an alternative to live animals.

Animal Testing Alternatives↗