Biomedical subjects

G Damien

Publications and source records attributed to G Damien.

5 recordsLinked to original sources

PubMed1999

Galenic development and pharmacokinetic profile of indapamide sustained release 1.5 mg.

In accordance with international guidelines recommending the use of low doses of antihypertensive agents, a new formulation of indapamide--indapamide sustained release (SR)--has been developed. Indapamide has been used worldwide for many years as an immediate release (IR) formulation at a dose of 2.5 mg. The IR formulation leads to plasma peaks of indapamide immediately after administration of the tablet. These peaks are responsible for possible unfavourable electrolyte or metabolic effects relating to indapamide blood concentrations. The SR formulation, by eliminating plasma peaks, allows a smoothing of the pharmacokinetic profile of indapamide. This new galenic formulation is based on a hydrophilic matrix tablet composed of a cellulose derivative, methylhydroxypropylcellulose (MHPC), and a binder, polyvinylpyrrolidone (povidone). The originality of the matrix lies in the percentages of MHPC and povidone, which permit a linear release in vitro of indapamide. After optimisation, the chosen ratio of these 2 constituents allowed the release of more than 70% of the dosage over 16 hours in a very reproducible manner. The 2 tested formulations (SR and IR) have the same bioavailability; however, the main pharmacokinetic parameters of the new SR 1.5 mg formulation, calculated after single and repeated administration, show a profile typical of an SR formulation, i.e. a lower maximum concentration (Cmax), a longer time to Cmax, and the same minimum concentration as the IR formulation. This new SR formulation, which allows a reduction in the daily dose of indapamide from 2.5 to 1.5 mg, leads to an improvement in its efficacy/tolerability ratio, thereby meeting the recommendations of the international guidelines for the treatment of essential hypertension.

Biological Availability↗

PubMed1993

[Acute arterial mesenteric ischemia].

The authors report the experience of their surgical department, in the treatment of acute arterial mesenteric ischemia. They insist on the diagnostic, and sometimes therapeutic, interest of mesenteric arteriography. Arterial revascularisation must be the surgical aim. In spite of this attitude, the prognosis of acute mesenteric ischemia remains very severe.

Adult↗

PubMed1992

Synthesis and ACE inhibitory activity of the stereoisomers of perindopril (S 9490) and perindoprilate (S 9780).

Perindopril, a powerful ACE inhibitor contains 5 chiral carbons, thus there is the possibility of 2(5) = 32 stereoisomers for the general structure 1. These 32 stereoisomers were synthesized by cross-coupling the 8 stereoisomers of perhydroindole 2-carboxylic acid benzylester with the 4 stereoisomers of 2-(1-carbethoxybutylamino) propionic acid 4, then hydrogenating the resulting benzylesters. Each stereoisomer of perindopril furnished by saponification the corresponding diacid stereoisomer 2 of perindoprilate which is the active form of perindopril. For each of the 32 stereoisomers 2 the in vitro ACE inhibitory potency (IC50) was determined. Four of them, including perindoprilate, had activities in the nanomolar range, and four more were ca. 10 x less active. The four acid esters 1 corresponding respectively to the four most active diacids 2 in vitro were studied (1 mg/kg via the oral route) for their in vivo activity in dogs. It could be concluded that p.o. absorption of the active acid esters 1 and their activation to the active diacid 2 depended only on the chiralities of the two ring junction carbons of the perhydroindole ring.

Administration, Oral↗

PubMed1989

Liquid chromatography-mass spectrometry of trace compounds with a moving-belt interface and multi-dimensional chromatography.

A high-performance liquid chromatographic method with on-line mass spectrometric detection is described for the structural analysis of a number of synthetic impurities, present at trace levels in almitrine. To obtain mass spectra with various ionization methods and high-resolution mass measurements, a moving-belt liquid chromatograph-mass spectrometer interface is used. A two-column switching system allows the injection of large amounts of almitrine, from which the trace compounds are trapped on a second column, while discarding the major component. This permits the introduction of the impurities into the mass spectrometer by elution of the second column, without the risk of introducing too large an amount of the major compound into the mass spectrometer. The mass spectra thus obtained are of sufficient quality to permit a correct structural assignment of the impurities.

Chemical Phenomena↗

PubMed1988

Analysis of almitrine and its metabolites in plasma using on-line fast atom bombardment liquid chromatography/mass spectrometry.

To validate a recently developed liquid chromatography/ultraviolet (LC/UV) method in a pharmacokinetic study of Vectarion (almitrine) where the unchanged drug, its five metabolites and an internal standard are analysed, on-line fast atom bombardment liquid chromatography/mass spectrometry (FAB LC/MS) with a moving belt interface has been used. Since the liquid chromatographic conditions required the use of perchloric acid FAB was chosen as ionization mode for the involatile perchlorates formed in the liquid chromatographic process. The use of FAB LC/MS allows the detection of the protonated molecular ions of all the components in the mixture. Furthermore, all the compounds show an intense peak at m/z 203, presenting a liquid chromatographic profile which is very similar to the profile obtained with UV detection.

Almitrine↗