Biomedical subjects

T Hulot

Publications and source records attributed to T Hulot.

6 recordsLinked to original sources

PubMed1998

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations.

In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300 (300 mg), Adizem XL (300 mg), Cardizem (300 mg) and Dilacor (240 mg). Sixteen healthy male volunteers (aged 22.9 +/- 3.3 years, range 19-31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (cmin), the maximum plasma concentration (cmax), the time to reach that concentration (tmax), the time interval during which the plasma concentration exceeds 50% of cmax (t50), the area under the plasma concentration-time curve (AUC72-96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC72-96 (AUCNDM and AUCDAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng.mL-1 in the morning hours were observed for Dilacor (240 mg) and Adizem XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.

Adult↗

PubMed1998

Clinical pharmacokinetics of acamprosate.

Acamprosate is a new psychotropic drug used in the treatment of alcohol (ethanol)-dependence. Recent studies suggest that acamprosate inhibits neuronal hyperexcitability by antagonising excitatory amino acids. It is available as a 333 mg enteric-coated tablet, with a recommended dosage of 1.3 g/day for patients with a bodyweight < 60 kg and 2 g/day for patients with a bodyweight > or = 60 kg. Treatment with higher dose strength tablets 2 x 500 mg twice daily is bioequivalent to treatment with the 2 x 333 mg 3 times daily dosage regimen. Acamprosate is absorbed via the paracellular route in the gastrointestinal tract. Absorption is rapid but limited after oral administration. At steady-state, acamprosate has a moderate distribution volume of about 20L. Acamprosate is not protein bound or metabolised. Half of the elimination of acamprosate occurs as unchanged acetyl-homotaurine in urine, the other half might be eliminated by biliary excretion. The administration of the enteric-coated tablets showed a flip-flop mechanism with a terminal elimination half-life 10-fold higher than the 3-hour half-life reported after intravenous infusion. During repeated oral administration of 666 mg 3 times daily, steady-state is reached after 5 to 7 days and leads to plasma concentrations ranging from 370 to 650 micrograms/L. The pharmacokinetics of acamprosate administered as an enteric-coated tablets are time- and dose-independent, and its accumulation ratio is about 2.4 at steady-state. Acamprosate disposition does not differ between males and females. The pharmacokinetics of acamprosate are not modified in patients with hepatic insufficiency or chronic alcoholism. In contrast, renal insufficiency influences the elimination of acamprosate and it is, therefore, contraindicated under such circumstances. Interaction studies have confirmed that when acamprosate is concomitantly administered with food, the amount absorbed is decreased. When combined with diazepam, disulfiram or alcohol, the pharmacokinetic disposition of acamprosate is not modified. Acamprosate does not influence the kinetics of diazepam, alcohol or imipramine and its metabolite desipramine.

Acamprosate↗

PubMed1998

Influence of age on the pharmacokinetics of naftidrofuryl after single oral administration in elderly versus young healthy volunteers.

The aim of this study was to evaluate and compare the pharmacokinetics of naftidrofuryl (CAS 3200-06-4) after single oral administration of a 200 mg naftidrofuryl tablet (Praxilene) in Caucasian male and female elderly healthy volunteers versus young healthy volunteers. Thirty healthy volunteers were included in a randomised phase I trial in 3 parallel groups of 10 subjects aged 18-35 years (group 1), 60-70 years (group 2) and 70-80 years (group 3). Blood samples were taken over a period of 24 h after dosing for evaluation of the pharmacokinetics of naftidrofuryl. The Cmax, tmax, AUC0-t parameters were measured and t1/2 and AUC0-alpha were calculated by a model independent method. The mean (+/- SD) pharmacokinetic parameters of naftidrofuryl after single oral administration of 200 mg of naftidrofuryl for group 1 were as follows: tmax 3.5 h (median), Cmax 284 +/- 136 ng/ml, t1/2 3.69 +/- 1.30 h, AUC0-t 1865 +/- 905 h.ng/ml and AUC0-inf 2055 +/- 901 h.ng/ml; for group 2: tmax 2.75 h (median), Cmax 282 +/- 165 ng/ml, t1/2 3.03 +/- 1.08 h, AUC0-t 1783 +/- 1147 h.ng/ml and AUC0-inf 1856 +/- 1158 h.ng/ml; for group 3: tmax 2.5 h (median), Cmax 271 +/- 86 ng/ml, t1/2 3.50 +/- 1.29 h, AUC0-t 1742 +/- 544 h.ng/ml and AUC0-inf 1834 +/- 549 h.ng/ml. Statistical analysis was performed on the pharmacokinetic parameters with one-way ANOVA in order to compare each age group. The results of the pharmacokinetic and statistical analysis showed no significant difference between each age group. The mean pharmacokinetic parameters of naftidrofuryl after single oral administration of 200 mg of naftidrofuryl in the whole population were as follows: tmax 2.75 h (median), for Cmax 279 +/- 128 ng/ml, t1/2 3.41 +/- 1.22 h, AUC0-t 1797 +/- 870 h.ng/ml for AUC0-inf 1910 +/- 877 h.ng/ml. In conclusion, advanced age did not appear to influence the pharmacokinetic profile of oral naftidrofuryl, and therefore it is not necessary to adjust the dosage of naftidrofuryl in this population.

Administration, Oral↗

PubMed1991

An original intragastric delivery system for oral administration of solid formulations to fully conscious rats: its application to oxodipine studies.

The purpose of this paper is to describe an original intragastric delivery system for powders to conscious rats. This system is an administration cannula composed of a simple polypropylene tube, long enough to reach the stomach and an adapted metallic stem in the lumen of the tube. A finite dose of powder, set on the free extremity of the cannuly, is expulsed into the stomach. This delivery system is applied to study oxodipine absorption from oral solid forms containing appropriate vehicles. Different test formulations were administered to rats: solution by I.V. (1 mg/kg) and P.O. (2mg/kg) routes, and oral dry powders (2 ng/kg). Blood samples were collected until 12 hours post-dose. Oxodipine plasma levels are measured by a HPLC method. Results indicated that the rate and extent of absorption can be modulated by the administration of oxodipine in different formulations. The formulations studied can be classified as a function of the vehicles added to the solid formulation. In fact, the limiting factor of absorption in rats is the in vivo dissolution rate. Absolute bioavailability can be modulated by different formulations. The apparent elimination half-life was dependent on the dissolution rate of oxodipine from formulations.

Administration, Oral↗

PubMed1990

Disposition and metabolism of two acetylcholinesterase reactivators, pyrimidoxime and HI6, in rats submitted to organophosphate poisoning.

1. The dispositions of two acetylcholinesterase reactivators, pyrimidoxime and HI6, labelled with 14C on the oxime group, have been studied in normal rats and rats poisoned by the organophosphates Soman and A4. 2. For both compounds, and for healthy and poisoned rats, radioactivity was eliminated essentially in the urine (85% dose in 24 h). Faecal elimination was low (4% in 72 h). 3. Both compounds were concentrated in kidney and mucopolysaccharide-containing tissues such as cartilage and intervertebral disc. Soman and A4 poisoning do not modify the kinetic parameters of pyrimidoxime, but A4 poisoning increases HI6 tissue concentration. 4. Chromatography of urine and plasma showed only unchanged pyrimidoxime in both healthy and poisoned animals. In contrast, HI6 in plasma and urine was strongly degraded by scission of the quaternary ammonium bond, and formation of 2-pyridine aldoxime.

Acetylcholinesterase↗

PubMedDate not supplied

LIMS: from theory to practice.

This paper gives a definition and some basic knowledge about Laboratory Information Management Systems (LIMS) as well as their impact on the organisation, the laboratory and the co-workers. The major advantages and disadvantages of LIMS are pointed out. Two practical experiences are described. The first is related to an in house development of a PC based system which has to integrate a Vax VMS system (Multichrom) and PC based analytical and analysis softwares. The second experience is dealing with the selection and implementation of a commercial package in a pharmacokinetic laboratory. In both cases the human and time aspects were important.

Clinical Laboratory Information Systems↗