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Biomedical subjects

M Ollagnier

Publications and source records attributed to M Ollagnier.

At least 37 records · Page 2Linked to original sources
PubMed1992

[Chronopharmacology of fractionated heparin (nadroparin) administrated by subcutaneous route at prophylactic doses in healthy volunteers].

This study evaluated the effect of injection time on pharmacodynamic of a single subcutaneous bolus of nadroparine (7500 anti-Xa IC U) evaluated by anti-Xa activity (Hepaclot and Heptest) and by activated partial thromboplastin time (APTT by auto PTT reagent). 10 healthy male volunteers were studied at 4 different 24 hours periods with 4 different injection times (6 am, 12 am, 6 pm, 12 pm) and with a one week wash-out period between each period. No chronopharmacological variation of the anti-Xa activity evaluated by Hepaclot was found. However the anti-Xa activity evaluated by Heptest was higher at the sixth hour after 12 am injection (p = 0.0022). No difference on APTT values was observed whatever the injection time. So the injection time of nadroparine has a weak influence on anti-Xa activity and no effect on APTT; Before to conclude on the lack of chronopharmacological effect of nadroparine, it seems necessary to evaluate such a possibility with higher dosage, with sick and older subjects.

Adult↗
PubMed1992

[Study of serum kinetics of vancomycin during the "antibiotic-lock" technique].

The serum kinetics of vancomycin was studied in two patients aged 3 and 15 years during antibiotic therapy for catheter related sepsis associated with Staphylococcus epidermidis. Vancomycin was administered, simultaneously, by parenteral conventional doses (30 mg/kg/day div q 8 h) and using the antibiotic-lock technique in the infected catheter at a high concentration (150 mg/ml) during one hour, 3 hours after each infusion. Pharmacokinetics data did not show any significant change in the serum kinetics of the antibiotic. The results suggest that delivering a high concentration of vancomycin in the infected catheter using the lock technique may be useful to sterilize infected catheter without toxic effect.

Adolescent↗
PubMed1990

Good clinical practices in phase I studies.

In France, official guidelines for good clinical practices in clinical trials were issued in 1987. In December 1988, a law was passed that fixed the requirements for carrying out experiments in healthy subjects. It will be completed by official guidelines for the structures in which experiments on healthy subjects (and patients as well, when the investigation would not benefit the health of the patients) may be conducted. Hence a battery of recent legal instructions precisely state what good clinical practices are in the setting of phase I studies. Of particular importance are: subject recruitment and selection methods and procedures; specific competence of the investigator, in particular to interpret the pre-trial data; necessary and sufficient facilities to guarantee the subjects' safety; careful quality control to check all laboratory procedures; necessity of written standard operating procedures.

Drug Evaluation↗
PubMed1987

Circadian changes in the pharmacokinetics of oral ketoprofen.

Several investigations which have taken treatment time into account have shown that the pharmacokinetic parameters, the therapeutic efficacy and even the toxicity of a large number of products may vary according to the administration schedule. The present study was carried out in order to evaluate any circadian changes in pharmacokinetic parameters of ketoprofen, a new non-steroidal anti-inflammatory drug (NSAID). This randomised crossover study consisted of a single oral dose of ketoprofen 100mg administered to 8 healthy male volunteers, mean age 27.2 years, at 07.00 hours, 13.00 hours, 19.00 hours or 01.00 hours in 4 study periods during the first 3 months of the year. The order of administration was randomised, with each subject acting as his own control. A total of 14 blood and 4 urine samples were taken over a 12-hour period. The peak plasma concentration was twice as high after drug administration at 07.00 hours (13.4 +/- 1 mg/L) than after other administration times (13.00 hours: 6.9 +/- 1; 19.00 hours: 7.2 +/- 0.7; 01.00 hours: 6.3 +/- 0.5 mg/L) [p less than 0.001]. The time to reach peak concentration was much longer after drug administration at 01.00 hours (135 +/- 16.7 min) than at 07.00 (73.1 +/- 14.1 min), 13.00 (75 +/- 16.5 min) or 19.00 hours (82.5 +/- 12.7 min) [p less than 0.05]. The lag time was significantly longer at 01.00 hours than at 13.00 hours (p less than 0.01). The absorption rate constant after treatment at 01.00 hours was less than at the other times of administration (p less than 0.05). The bodyweight-corrected area under the curve (AUC0-12) was greater after 07.00 hours than after 13.00 (p less than 0.01) or 19.00 hours (p less than 0.05) and greater after 01.00 hours than after 13.00 hours (p less than 0.05). The elimination half-life was significantly longer after administration at 01.00 hours than after 19.00 hours (p less than 0.05), while the total clearance was lowest at 07.00 hours. Cosinor analysis demonstrated statistically significant circadian rhythms for all pharmacokinetic parameters described above. The amount of ketoprofen eliminated in the urine was delayed, and was significantly greater after the administration at 01.00 hours than 07.00 hours or 19.00 hours (p less than 0.01). The relationship between absorption, diffusion and/or elimination mechanisms of the drug are discussed.

Administration, Oral↗
PubMed1987

[Biological rhythm and thromboembolic disease. Physiological, epidemiological and pharmacological aspects].

Arterial and venous thromboembolic disorders are the leading cause of death in most of the advanced nations. The study of physiologic, epidemiologic and pharmacologic relationships of these disorders to biological rhythms, may lead to a better understanding and perhaps a better treatment. Chronophysiologic studies have shown that hemostatic variables follow circadian rhythms. The level of platelets aggregation and of blood coagulation has been found to be increased in the morning and decreased at night, whereas fibrinolytic activity is lower in the morning than in the evening. Chronoepidemiologic studies demonstrated a morning peak for arterial thromboembolic disorders and an evening peak for cerebral bleedings. These facts might partially be explained by circadian variations in hemostasis and suggest a chronotherapeutic approach in thromboembolic disorders. Unfractionated heparin, because of its antithrombotic effect, is one of the major drugs used to treat this disease. However, with such a treatment venous thrombosis recurs or bleeding complications occur yet in about 30% of patients. Chronopharmacologic studies indicate that anticoagulant effect of heparin is minimum in the morning and maximum at night, following the physiologic circadian variation of blood coagulation. Such results suggest that the heparin doses should be modulated as a function of administration times in order to increase its effectiveness and to minimize both bleeding risk and thrombosis. Further studies are needed to evaluate such a proposal.

Biological Clocks↗
PubMed1985

[Chronokinetics of ketoprofen administered orally and by continuous venous infusion].

The aim of the study was to evaluate a possible chronokinetic phenomenon of ketoprofen administered orally and by continuous intravenous infusion. In the first part of the study, ketoprofen was administered orally to 8 healthy male volunteers aged between 25 and 45 years, at a dose of 2 X 50 mg at 7:00 a.m. (time I), 1:00 p.m. (time II), 7:00 p.m. (time III) and 1:00 a.m. (time IV), on the same day of the week at an interval of 2 weeks, during the first three months of the year. The order of administration was randomised, each subject acted as his own control and received ketoprofen at the four times mentioned above. A total of 14 venous blood samples were taken over 12 hours. The results indicate that the maximal serum concentration (Cmax) was significantly higher at time I (13.4 +/- 14.1) than at times II, III and IV (6.9 +/- 1.1, 7.2 +/- 0.7, 6.4 +/- 0.5 mg/l) (p less than 0.01). The time required to reach this concentration (Tmax) was significantly longer for time IV (135.0 +/- 16,8) than for times I, II and III (73,1 +/- 14.1, 75,0 +/- 16.6; 82.5 +/- 12.7 minutes) (p less than 0.05). The excretion half-life (t 1/2B) was significantly longer for time IV (4.3 +/- 0.6) than for times II and III (2.8 +/- 0.5, 2.5 +/- 0.2 hours) (p less than 0.05). Statistically significant differences were also observed in the area under the curve measured at midday (AUC 12) and in the total clearance (CIT) for the various sample times.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

[Post-anesthetic hepatitis. The role of halothane and antimitotic combinations].

A 12 year old boy with Burkitt's lymphoma developed severe hepatitis with hepatomegaly, subclinical jaundice, and a small rise in body temperature, associated with an important rise in SGPT and fall in prothrombin titres, 6 days after anticancer chemotherapy and 24 hours after halothane anaesthesia. Hepatitis A and B serology remained negative. This hepatic failure explained perhaps the unusually severe vincristine toxicity which gave rise to a polyneuritis with important sequelae. The association of halothane hepatitis with antimitotic drugs appeared particularly dangerous, and halothane should probably be avoided in all patients been given or about to be given anticancer chemotherapy.

Anesthesia, Inhalation↗
PubMed1984

[Neutropenia from oxacillin. 3 pediatric cases].

Neutropenia developed in 3 pediatrics patients during treatment with oxacillin. The time of onset ranged from 18 to 24 days after beginning treatment with dose of 150 mg/kg/24 h. Concomitant symptoms were fever and rashes. During treatment with oxacillin it is necessary to monitor blood cell count every week.

Adolescent↗
PubMed1983

[Influence of tobacco on the serum levels and pharmacokinetics of phenylbutazone and oxyphenbutazone].

The serum levels of a number of drugs are reduced by smoking. The authors wanted to see whether this phenomenon occurred with phenylbutazone. With this objective, they compared the changes in serum levels of phenylbutazone and oxyphenbutazone, the hydroxylated metabolite of phenylbutazone, during ten days of administration, in 9 smokers and in 6 non-smokers. Blood samples were taken every day at 8:00 a.m. and the PB and OPB were assayed by high performance liquid chromatography. The comparison of the mean serum levels of PB in smokers and non-smokers revealed a statistically significant reduction (p less than or equal to 0.05) of this level in the smoker, between D5 and D10. Comparison of the mean serum levels of OPB in smokers and non-smokers revealed a statistically significant reduction of this level in the smoker, but only on days 9 and 10. When we compare these results with those reported in the literature for other drugs, it would appear that tobacco smoke accelerates the metabolism of phenylbutazone and oxyphenbutazone by a mechanism of enzyme induction. It is proposed that the therapeutic activity of phenylbutazone is reduced in the smoker, but this has not been confirmed by a reliable clinical evaluation in this initial study.

Adult↗
PubMed1981

A comparison of the myocardial depressant effects of several aminoglycoside antibiotics.

The myocardial depressant action of aminoglycosides has been known for a number of years but there was no available data on newer derivatives. We have thus studied the contractile responses of isolated guinea pig left atria to increasing concentrations of gentamicin, tobramycin, lividomycin and amikacin (0.02, 0.04, 0.08, 0.13, 0.17 and 0.22 mM). Our results are consistent with those of previous workers and show that newer aminoglycosides do exert a similar depressant action. As gentamicin and tobramycin are more depressant than lividomycin, then amikacin at similar concentrations, no clear-cut difference was obtained when respecting a relative range of concentrations mimicking that of clinical situations. However, these depressant effects were attained using concentrations far exceeding those reached in man.

Amikacin↗
PubMed1981

[Electrophysiological study of cardiac effects of succinylcholine: role of vagal tone and hyperkalemia in anesthetized dog (author's transl)].

The effects of intravenously infused succinylcholine (SCh): 1 mg/kg/minute during 30 minutes were assessed in anesthetized dogs on spontaneous heart rate, conduction within the atrio-ventricular node and the His-Purkinje system and on atrial (AERP) and atrio-ventricular (AVERP) effective refractory periods with varying levels of vagal tone and under mild hyperkalemia. 1) The heart rate which was not affected by SCh in the absence of vagal tone was by contrast increased by 50 p. cent when vagal tone was maintained. Under hyperkalemia, the vagolysis-mediated tachycardia did not prove more marked. 2) The conduction velocity, which was never modified by SCh in either the atria or the His-Purkinje system, was always accelerated with vagal tone. This acceleration is directly related to the vagolytic properties of SCh, but also partly to a mild hyperkalemia. The changes of potassium blood levels tend to reverse the potassium outflow due to the parasympathetic neuromediator. 3) The AERP was was lengthened by SCh and hyperkalemia; the latter impaired the outflow of potassium ions responsible for repolarization. The AVERP was always shortened when the vagal tone is maintained, however less largely under mild hyperkalemia which limits SCh anticholinergic effect owing to its own anticholinergic action.

Anesthesia, General↗
PubMed1980

Effects of mild hyperkalemia on conduction velocity and effective refractory period in various parts of the dog heart in situ.

Effects of mild hyperkalemia on conduction velocity, effective refractory periods (ERPs) and sinus rate were studied on 16 anesthetized dogs, using endocavitary His bundle recordings, the extrastimulus method and standard electrocardiogram. Six dogs were placed under acetylcholine infusion (300 micrograms/kg/min) (ACh group), 10 received atropine sulfate 0.2 mg/kg intravenously (atropine group). Intraventricular conduction time, ventricular ERP and QRS duration of the EKG were studied on 7 other open-chested dogs (ventricular group). During a 60 min potassium chloride infusion (0.025 mmol/kg/min, 30 min, then 0.05 mmol/kg/min, 30 min), following observations were made: - In the ACh group, AV node conduction time (A-H interval) decreased by 20% and AV node ERP by 17%, whereas, in the atropine group, the former parameter was not affected and atrial ERP increased by 29%. - At the same time, sinus rate increased in the ACh group and was unaffected in the atropine group. - Conduction times in atrial contractile tissue (S-A interval), His-Purkinje system (H-V interval) and ventricular contractile tissue, like ventricular ERP, exhibited no variation or very slight, occasionally biphasic variations under both conditions. These results can be accounted for by an "anticholinergic" effect of mild hyperkalemia which is discussed.

Animals↗
PubMed1980

Inhibition by idrocilamide of the disposition of caffeine.

The pharmacokinetics of caffeine are greatly altered by concomitant administration of idrocilamide. In four healthy volunteers id rocilamide inhibited the biotransformation of caffeine and increased its half-life nine times. The untoward neuropsychiatric effects of idrocilamide are the consequence of abnormal accumulation of caffeine in regular consumers of caffeine-containing foods and beverages.

Adult↗