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Biomedical subjects

M J Royer-Morrot

Publications and source records attributed to M J Royer-Morrot.

At least 19 recordsLinked to original sources
PubMed1996

Penetration of pefloxacin and its desmethyl metabolite into the uroepithelium after a 800-mg single oral dose in human patients.

Penetration of pefloxacin into the uroepithelium was studied in 20 patients (10 men and 10 women) receiving a single oral dose of 800 mg. Samples of serum, urine, and uroepithelium were taken 1.8 h (mean) after the dose. Pefloxacin and its active metabolite, norfloxacin, were assayed by liquid chromatography, and the microbiologically active compounds were quantified by a microbiological assay. Both procedures were correlated (r > 0.7); nevertheless, slight differences detected in concentrations depended on the levels of norfloxacin achieved in the biological samples. The serum and tissue concentrations were higher than the concentration of bactericide (4 micrograms.ml-1), except in one case. The uroepithelium concentration of pefloxacin was proportional to the serum concentration (r = 0.79). The urinary concentrations ranged from 1.2 micrograms.ml-1 to 82.4 micrograms.ml-1. The mean norfloxacin/pefloxacin ratios were 3% in serum, 8% in uroepithelium, and 44% in urine. The mean uroepithelium/serum concentration ratios were 1 for pefloxacin and 2.3 for norfloxacin. This result shows that, at a time close to that of the maximum concentration, there is good penetration of pefloxacin and norfloxacin into the uroepithelium.

Administration, Oral↗
PubMed1994

A double Weibull input function describes the complex absorption of sustained-release oral sodium valproate.

The pharmacokinetics of valproic acid after oral administration of sustained-release formulations were studied in 12 healthy volunteers. The objective of the present study was to find an appropriate mathematical model to describe the complex drug intake process. The concentration of valproic acid in plasma was measured by HPLC. For each subject, during the input process a double peak phenomenon was observed, the plasma concentrations were fitted according to a single or a double Weibull input function, and then a first-order elimination rate was used to describe the observed data. The Weibull model was considered as an approximation of the overall process. The mean peak plasma concentration, 34.6 +/- 8.9 mg/L, was reached after 8.6 +/- 2.7 h. A single Weibull function adequately described the observed data for three subjects; the mean Weibull parameters were td (the time necessary to transfer 63% of the administered drug into the systemic circulation) of 7.87 +/- 3.53 h and gamma (shape) of 1.16 +/- 0.66. A double Weibull input function was used for nine subjects; the mean Weibull parameters were td1 = 2.35 +/- 1.18 h and td2 = 9.36 +/- 4.47 h and gamma 1 = 1.77 +/- 2.27 and gamma 2 = 3.68 +/- 3.26. The mean half-life value of the elimination phase was 14.4 +/- 4.6 h.

Absorption↗
PubMed1993

Influence of food intake on the pharmacokinetics of a sustained release formulation of sodium valproate.

The effect of food intake on the pharmacokinetics of DEPAKINE CHRONO 500 mg (Sanofi, France), a sustained release formulation containing 333 mg sodium valproate and 145 mg valproic acid, was studied in 12 young healthy female volunteers. Relative to fasting conditions (F), when the tablet was given at the midpoint of the breakfast (NF), the maximum concentration (F: 34.6 +/- 8.9 micrograms ml-1 and NF: 40.9 +/- 7.3 micrograms ml-1; p = 0.014) and the mean cumulative amount absorbed up to time 6 h (F: 76.3 +/- 11.8% and NF: 90 +/- 10.4%; p = 0.0099) were significantly increased. Nevertheless, the extent of absorption (F: 46.7 +/- 9.9 mg l-1; NF: 48.7 +/- 7 mg l-1) was not significantly affected. There was no change in the area under the curve (1129 micrograms.h ml-1), in the mean residence time (28 h), or in the elimination half-life (16 h). On the basis of this study, the question as to whether DEPAKINE CHRONO should be administered to subjects in the fasting or non-fasting state would not appear to be a major consideration when deciding on the regimen.

Adult↗
PubMed1992

Determination of zopiclone in plasma using column liquid chromatography with ultraviolet detection.

A reversed-phase liquid chromatographic method with ultraviolet detection for the determination of zopiclone in plasma is described. It is rapid, sensitive, reproducible and linear over a wide range. The method was used to study plasma zopiclone concentrations in a case of acute intoxication after oral ingestion of 300 mg of the drug. The plasma level was 1600 ng/ml 4.5 h after the dose and the elimination half-life was 3.5 h.

Adult↗
PubMed1992

Plasma thiamine concentrations after intramuscular and oral multiple dosage regimens in healthy men.

A novel liquid chromatographic method for the determination of thiamine in plasma has been developed and has been used to study plasma thiamine concentrations after multiple dosage regimens for 11 days. The method involves purification, concentration and analytical separation of thiochrome on-line, using a switching column system. Ten healthy men were given 500 mg thiamine i.m. once a day (Group 1) and ten were given 250 mg p.o. every 12 h (Group 2). The times to reach steady state (7 and 5.6 days for Groups 1 and 2, respectively) were not different (P greater than 0.05). The mean elimination half-life was 1.8 days. The mean minimum steady-state concentration after the oral regimen (23 micrograms.l-1) was 78% of that after the intramuscular regime (29 micrograms.l-1).

Administration, Oral↗
PubMed1991

Effect of plasma exchange on flumequine pharmacokinetics: comparison with control kinetics.

The effect of plasma exchange (PE) on the pharmacokinetics of flumequine (Apurone) was studied in eight patients receiving a single oral dose of 800 mg. The maximum concentration (38 micrograms/ml) and time to maximum concentration (2.6 h) values were not significantly altered by PE beginning 3 h after administration of flumequine. There was no change in the terminal elimination half-lives (6.6 h), in the steady-state volume of distribution (29 L), or in the apparent plasma clearance (2.5 L/h). By contrast, PE decreased the mean residence time by 30% (14.3 +/- 4.1 h without PE; 9.88 +/- 1.36 h with PE; p less than 0.05). The amount of flumequine extracted by PE (72 mg) was proportional to the plasma concentration at the beginning of the exchange. The elimination half-life during PE (3.15 +/- 1.23 h) decreased by 40%. Renal clearance (0.3 L/h) was not affected. PE only partially modifies the pharmacokinetics of flumequine administered in a single oral dose before PE.

Administration, Oral↗
PubMed1989

Tianeptine and its main metabolite pharmacokinetics in chronic alcoholism and cirrhosis.

The effect of chronic alcoholism (with or without associated moderate cirrhosis) on the disposition of the antidepressant tianeptine, which is devoid of substantial first-pass metabolism, was examined in 21 patients and 11 age-matched controls. Pharmacokinetic parameters for tianeptine and its C5 acid analogue metabolite (MC5 metabolite) were estimated by non-compartmental analysis. The area under the curve (AUC) for tianeptine, following a 12.5mg single oral dose, was decreased by 31% in chronic alcoholics and increased by only 14% in cirrhotics, compared to controls. These changes did not attain statistical significance. The trend of changes in the AUC for the MC5 metabolite was similar to that observed for the parent drug. No statistical difference was found in the terminal half-life for both tianeptine and its MC5 metabolite between patients and controls. On the basis of this study, it appears unnecessary to modify the proposed dosage regimen used in clinical trials (tianeptine sodium salt 12.5mg 3 times daily) in chronic alcoholics with or without associated moderate cirrhosis.

Adult↗
PubMed1989

Recent findings on the pharmacokinetics of non-steroidal anti-inflammatory drugs in synovial fluid.

Synovial fluid concentration is considered to be an important determinant of clinical response to non-steroidal anti-inflammatory drugs (NSAIDs). Trans-synovial transport of these drugs is a process of limited diffusion, governed partly by the pharmacological characteristics of NSAIDs and partly by the properties of the joint and joint space themselves. The studies which report simultaneous pharmacokinetics of NSAIDs in both plasma and synovial fluid compartments are of 2 types: (1) some compare the concurrent concentrations of drugs in plasma and joint fluid after a single administration. These provide pharmacokinetic information: (2) others, which conform more closely to the therapeutic conditions, look at synovial fluid and plasma concentrations after repeated administration of the drug. Recent findings on the pharmacokinetics of NSAIDs in synovial fluid are reviewed. These studies reveal 2 types of NSAIDs, according to their pharmacokinetic behaviour. First, there are NSAIDs with a short or intermediate plasma elimination half-life. These drugs equilibrate rapidly relative to their elimination; their peak synovial fluid concentrations occur later and are lower than those in plasma. Several hours after administration there is crossover of the concentration curves, and beyond this point, concentrations in synovial fluid may exceed those in plasma. During prolonged treatment, the synovial fluid concentrations of these NSAIDs fluctuate to a much lesser extent than plasma concentrations. Secondly, there are NSAIDs with a long plasma elimination half-life; their peak concentration in synovial fluid is also lower and later than that in plasma. At steady-state their concentrations (total and free) in synovial fluid are about half those in plasma. Numerous variables must be taken into account in attempts to correlate synovial fluid NSAIDs concentrations with clinical response, including protein binding and determination of both active metabolites and (eventually) the enantiomers.

Animals↗
PubMed1987

Conversion from intravenous to oral slow-release disopyramide in acute myocardial infarction.

Twelve patients with acute myocardial infarction were given 1.5 mg/kg/5 min bolus +0.4 mg/kg/hr 6 hr IV infusion of disopyramide followed by 250 mg twice daily of a slow-release oral formulation of this drug. Plasma concentrations of total disopyramide rapidly reached steady-state within the therapeutic margins. The plasma steady-state concentrations of the major metabolite mono-N-dealkyl-disopyramide (MND) showed large intra-individual variations. There was no correlation between plasma levels of either disopyramide or MND and the occurrence of anticholinergic side effects. The drug had no significant effect on mean blood pressure, heart rate, or ECG intervals. This therapeutic regimen, including conversion from the IV form to oral slow-release tablets, could be recommended in myocardial infarction.

Adult↗
PubMed1976

[Pharmacokinetic data on phenobarbital. Study on the influence of gestational age and dysmaturity].

Blood levels of barbiturate after a single intramuscular injection of 10 mg of phenobarbiitone have been plotted against time in 15 neonates at term of whom five were normal and 10 were dysmature, and 15 pre-term infants between 32 and 34 wesks gestation, of whom 12 had a satisfactory weight and 3 were dysmature. The analysis of the experiments according to a mathematical model gave the following results. Half life of absorption +/- 1 S.D. 9.55 HR +/- 6.97 for the term neonates and 11.12 hr +/- 7.61 for the pre-term infants. The difference is not significant. Half life of elimination +/- 1 S.D. 118.06 hours +/- 64.79 for the neonates of term and 110.49 hr +/- 37.19 for the pre-term infants. The half life of elimination is much shorter in the pre-term dysmature infants 74.10 hrs +/- 40.12. The individual variations are important but the differences between the groups of neonates studied are not great. This permits re-grouping and calculation of a half life of elimination for the whole group of 114.28 hr +/- 28.05. The risk of over dosage and the large individual variation in the metabolism of phenobarbitone in the new born lead us to recommend checking the blood levels when giving repeated doses.

Birth Weight↗