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Y Le Roux

Publications and source records attributed to Y Le Roux.

43 records · Page 3Linked to original sources
PubMed1987

Critical factors for pharmacokinetics of zopiclone in the elderly and in patients with liver and renal insufficiency.

Zopiclone, a new hypnotic cyclopyrrolone, undergoes extensive hepatic metabolism. The carrier of hypnotic activity is the parent compound; however, knowledge of its metabolic profile is essential for the understanding of pharmacokinetic changes in various pathophysiological conditions. In 45 healthy young volunteers, zopiclone had a Tmax of 0.5. A first-pass effect of 20% resulted in an absolute bioavailability, F, of 77%. The volume of distribution ratio Vdc/Vdt was 3.2. The plasma half-life (t1/2) was 5.1 h. A metabolic ratio of 3.7 and 4.6 was found for the two main urinary metabolites, N-oxide and N-desmethyl derivatives. No modifications of kinetics were seen after chronic treatment. In eight patients with liver insufficiency, the main changes (delayed Tmax, 3.5 h, higher plasma concentrations with an increased F of 97%, prolonged t1/2 of 8.4 h) were essentially due to a reduced hepatic metabolic clearance, as shown by a decreased metabolic ratio for the two main metabolites. In 18 patients with renal insufficiency, the only major modification was an increased bioavailability (F of 115%) probably due to a relative decrease of the Vdc. In 19 elderly subjects, the main findings were a decreased metabolic clearance, as shown by decreased metabolic ratios, and an inversion of the Vdc/Vdt ratio, evoking the changes seen in renal insufficiency. The increase in F (168%) and the age-dependent increase in plasma t1/2 (8.1 h) in the oldest subjects (over 74 years of age) can be explained by this double mechanism. On the basis of these findings, a reduction of the initial zopiclone dose from 7.5 to 3.5 mg/day is recommended for patients with severe liver insufficiency and patients over 70 years of age with liver insufficiency.

Adult↗
PubMed1986

Pharmacokinetics of pefloxacin after repeated intravenous and oral administration (400 mg bid) in young healthy volunteers.

Multiple-dose kinetics of pefloxacin was determined in 12 normal male subjects given 400 mg pefloxacin by iv 1 h-infusion every 12 h for 16 doses. Twelve other subjects (6 men and 6 women) were given 400 mg pefloxacin by mouth every 12 h for 18 doses. Plasma and urine concentrations of pefloxacin and its main metabolites (N-desmethyl pefloxacin or norfloxacin and pefloxacin N-oxide) were measured by high performance liquid chromatography. The bioavailability of pefloxacin was complete and plasma concentrations after iv or oral administration were similar. Pefloxacin was rapidly absorbed from the gastrointestinal tract and reached maximum plasma concentrations about 1 h after dosing. Pefloxacin elimination (T 1/2 beta) increased from 11.00 +/- 2.64 h after the first iv dose to 13.93 +/- 3.58 h after the last iv dose (P less than 0.01). Apparent total body clearance decreased from 148.5 +/- 47.6 to 106.9 +/- 39.2 ml/min (P less than 0.01) because of decreased non-renal clearance (apparent volume of distribution did not significantly change over the repeated pefloxacin administration). Similar results were obtained after repeated oral dosing. Renal clearance of pefloxacin was low (7.47 +/- 2.28 ml/min) indicating that non-renal clearance represents the major route of elimination of this quinolone. Urinary excretion of pefloxacin and N-desmethyl and N-oxide metabolites was approximately 31% of the pefloxacin dose and beta-elimination half-lives of these metabolites were very close to that of pefloxacin (13.34 +/- 2.72 h and 11.95 +/- 2.64 h respectively). Due to a possible saturable process in the metabolic pathway, some accumulation occurred during repeated iv or oral treatment (accumulation ratio = 1.37 +/- 0.20). These results show that concentrations of pefloxacin in excess of the minimum inhibitory concentrations for many important pathogens can be rapidly achieved in plasma and urine with the 400 mg bid regimen with both iv and oral routes.

Administration, Oral↗
PubMed1979

Clinical pharmacology studies with acenocoumarol.

In two different studies, the relation between plasma concentrations of acenocoumarol and apparent prothrombin levels (Quick test) was investigated, using a new specific analytical method for the assay of the drug. The prothrombin level appeared independent of the plasma concentration of the drug, which is higher in old patients (over 70 years) than in younger patients (under 51 years).

Acenocoumarol↗
PubMed1977

Determination of acenocoumarol in plasma and urine by double radioisotope derivative analysis.

Acenocoumarol, to which a 14C-labeled internal standard has been added, is extracted at pH 4 into ethyl acetate-heptane (20:80 v/v), back-extracted into aqueous sodium hydroxide solution after solvent washing with a pH 7 buffer, and reextracted after acidification in the solvent mixture. It is then acetylated with 3H-acetic anhydride. The acenocoumarol acetyl derivative is separated from the metabolite derivatives by TLC, and its radioactivity is measured. The method is specific and sensitive to a concentration of 8 ng/ml.

Acenocoumarol↗
PubMedDate not supplied

Use of the repeated cross-over design in assessing bioequivalence: (within and between subjects variability - Schuirmann Confidence Intervals estimation).

In 1992, the Division of Bioequivalence in the Office of Generic Drugs published a guide to Statistical procedures for bioequivalence studies using a standard two-treatments cross-over design (1). This paper describes the application of the guidelines to a practical protocol and the recent Proc MIXED (SAS) will be shown to be much more convenient than the traditional Proc GLM for theoretical and practical reasons (correct estimation of residuals, analysis of the within-subjects variation, direct calculation of the Schuirmann 90% Confidence Intervals). This new procedure was applied to a study protocol on riluzole (Rilutek) including a replicate design with the within-subject and between-subject variances being estimated on Cmax and AUC biopharmaceutic parameters.

Administration, Oral↗