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Biomedical subjects

M Guyot

Publications and source records attributed to M Guyot.

At least 73 records · Page 4Linked to original sources
PubMed1984

Stiripentol kinetics in epilepsy: nonlinearity and interactions.

Stiripentol kinetics during oral therapy were assessed in six patients with epilepsy who were receiving other antiepileptic drugs. Steady-state levels at 600, 1200, and 2400 mg/day increased in a nonlinear fashion, indicating Michaelis-Menten kinetics. Oral clearance of stiripentol at 600 mg/day was 41.5 +/- 23.4 l/day/kg (mean +/- SD), greater than that at 1200 mg/day (20.3 +/- 8.8 l/day/kg; P less than 0.05) or 2400 mg/day (8.5 +/- 3.8 l/day/kg; P less than 0.01). The apparent in vivo Michaelis-Menten parameters were determined from three mean steady-state concentrations. The average velocity of conversion of stiripentol to its metabolites (Vm), Michaelis constant (Km), and the ratio Vm/Km were 49.3 +/- 13.1 mg/day/kg, 1.35 +/- 1.08 mg/l, and 50.2 +/- 27.5 l/day/kg. Stiripentol reduced the elimination clearances of concomitant antiepileptic drugs. Phenytoin clearance was reduced in all five subjects who received this drug, from a mean control of 29.5 +/- 13.4 l/day to 18.5 +/- 4.6 l/day at a stiripentol dose of 1200 mg/day (P = 0.05) and to 6.48 +/- 2.59 l/day at 2400 mg/day (P less than 0.01). Stiripentol reduced the clearance of carbamazepine in one subject from a control value of 209 l/day to 128 l/day (1200 mg/day) and 61 l/day (2400 mg/day). Stiripentol reduced phenobarbital clearance in two subjects from 3.8 and 5.1 l/day to 2.3 and 3.4 l/day (2400 mg/day). The Michaelis-Menten kinetics of stiripentol, as well as its interactions with other antiepileptic drugs, have important implications in the designing of controlled clinical trials.

Administration, Oral↗
PubMed1984

Michaelis-Menten kinetics of stiripentol in normal humans.

Michaelis-Menten kinetic parameters for stiripentol, and anticonvulsant, were assessed in six normal volunteers. Stiripentol was administered orally three times a day in dosage increments of 600, 1,200, and 1,800 mg/day for consecutive periods of 3, 4, and 7 days, respectively. Stiripentol steady-state levels at the three dosing rates increased more than proportionally with dose. The mean +/- SD oral clearance of stiripentol at 600 mg/day (1,090 +/- 624 L/day) was significantly greater (p less than 0.01) than at 1,200 (506 +/- 219 L/day) or 1,800 (405 +/- 151 L/day) mg/day. Average steady-state concentrations predicted from individually determined Vm and Km parameters were in good agreement with experimentally observed levels, indicating that the kinetics of stiripentol are of the Michaelis-Menten type. The mean Vm, Km, and Vm/Km ratio were 2,299 +/- 490 mg/day, 2.20 +/- 1.28 mg/L, and 1,241 +/- 837 L/day, respectively. Neuropsychological tests carried out before and after 14 days of stiripentol treatment showed a significant decline in verbal learning ability (p = 0.038) and a significant improvement in a test of memory and attention (p less than 0.01).

Adult↗
PubMed1984

Carbamazepine/valproic acid interaction in man and rhesus monkey.

Sodium valproate (VPA) was administered for 1 week (1 g b.i.d.) to seven epileptic patients receiving chronic carbamazepine (CBZ) therapy. Steady-state CBZ levels determined before and after VPA therapy were reduced by 3-59% in six patients and were unchanged in one patient. The plasma concentration ratio of carbamazepine-10,11-epoxide ( CBZE ) to CBZ increased in all patients by 11-500%. The plasma binding of CBZ was determined in six healthy volunteers given a single 400 mg CBZ dose with and without the coadministration of 1 g VPA in a cross-over design. The mean CBZ free-fraction was increased in three of the subjects (p = 0.008-0.031), decreased in one subject (p less than 0.002), and remained unchanged in two subjects when VPA was administered. Four male rhesus monkeys were infused intravenously with CBZ (15 mg h-1) for 5 days and then three consecutive 24-h infusions were given: I, CBZ alone; II, CBZ with 75 mg h-1 VPA; III, CBZ with 150 mg h-1 VPA. The mean free-fraction of CBZ and CBZE increased during infusions II and III from 31.5 +/- 2.7% to 33.6 +/- 2.6% (p less than 0.05) and 37.7 +/- 1.3% (p less than 0.01) for CBZ and from 46.9 +/- 9.2% to 53.6 +/- 5.7% (p greater than 0.05) and 60.1 +/- 4.0% (p less than 0.01) for CBZE . The clearance of free CBZ declined from 7.96 +/- 1.75 to 4.84 +/- 1.26 (p less than 0.01) and 4.12 +/- 1.75 (p less than 0.01) 1 kg-1h-1 during infusions II and III, respectively. The mean free CBZE /CBZ ratio increased from 0.12 +/- 0.03 to 0.24 +/- 0.03 and 0.36 +/- 0.04 during infusions II and III, respectively (p less than 0.001). These findings indicate a decrease in the elimination clearance of CBZE possibly coupled with a decrease in its formation clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

[Pharmacokinetics of apalcillin. Study of linearity].

Apalcillin is a new semi-synthetic penicillin active on the positive Gram bacteria, and on the enterobacteria, with a particular activity on Pseudomonas and Acinetobacter. The linearity study of the pharmacokinetic was carried out on 26 subjects who were given increasing doses (500, 1 000, 2 000, 3 000 mg) of apalcillin by the venous route. The dosages carried out by the HPLC and bacteriological methods, show a good correlation between the two methods. The serum concentrations, 5 mn. after injection, were respectively 72 micrograms/ml (500 mg); 145 micrograms/ml (1 g) ; 221 micrograms/ml (2 g) ; 290 micrograms/ml (3 g). Urinary excretion is around 20 %, and this, regardless of the dose. The dose increase seems to have no effect on the pharmacokinetic parameters, calculated on the basis of a bi- compartmental model. The areas under the time serum concentrations, increase proportionally, to the dose : 61 (500 mg) ; 146 (1 g) ; 285 (2 g) ; 367 (3 g) - micrograms/ml X h. the linear regression between the AUC (y) and the applied doses (X) is : y = 0,12 X + 14,27 ; r = 0,9046 ; n = 69. The correlation between the AUC and the doses is significant (p less than 0,001). The results obtained show that increasing the dosage has no effect on apalcillin pharmacokinetics, which appear linear.

Adult↗
PubMed1983

No effect of food intake on clobazam absorption.

The kinetics of clobazam taken 3 h before, during, and 3 h after a standard hospital meal were studied in six healthy volunteers. Peak plasma levels were significantly lower when the drug was taken with or after meals suggesting that the rate of absorption was reduced by food. The mean area under the concentration vs time curve was not affected by the time of drug administration indicating that the meal had no effect upon the extent of absorption.

Adult↗
PubMed1983

Double-blind crossover trial of progabide versus placebo in severe epilepsies.

In this double-blind, two-period, crossover trial with randomized treatment assignment, progabide (+/- 30 mg/kg/day) and placebo were compared as add-on to standard therapy in 20 "therapy-resistant" epileptic patients (11 males, nine females; age range, 7-47 years). The duration of each treatment period was 6 weeks. Crossover was performed gradually over 3-4 days. Twenty-four patients entered the study: three dropped out for reasons unrelated to progabide effects; one dropped out during the placebo period because of increased seizure frequency. Of the 20 patients who completed the study, 14 had partial, two partial plus secondary generalized, and four generalized seizures. Preexisting antiepileptic treatment consisted of one antiepileptic drug (AED) in three, two AEDs in eight, three AEDs in five, and four AEDs in four patients (mean, 2.5 AEDs/patient). The following parameters were recorded at biweekly intervals: (a) efficacy parameters--total seizure count, counts of each seizure type, and global clinical judgment; (b) safety parameters--adverse drug effects, brief clinical and neurological examinations, and laboratory tests; and (c) plasma concentrations of progabide and of the associated AEDs. Twelve patients were considered to be improved (p less than 0.01) with progabide by global clinical judgment compared with two patients improved with placebo. Nine patients of 20 had a 48-100% reduction of total seizure count in the verum period, leading to a significant reduction of total seizure number and of complex partial seizures in the verum period as compared with the placebo period (p less than 0.05). Adverse effects were reported or observed in 10 patients during the progabide period and in five patients in the placebo period. The side effects were generally mild and consisted of somnolence in four cases and of tremors, dry mouth, troubles of equilibrium, anorexia, euphoria, depression, and anxiety in individual patients; a 15-20% reduction of the progabide dose was required in two cases only. No treatment-related alterations in results of laboratory tests were observed.

Adolescent↗
PubMed1983

[Pharmacokinetic study of apalcillin after infusion].

Apalcillin is a new semi-synthetic penicillin of the uridino-penicillin group. The study comprises two groups of 6 subjects receiving 1 g and 2 g respectively of apalcilline by a two-hour infusion. The assays done by HPLC and microbiology show a good correlation between the two methods. The serum concentrations at the end of the infusion are: 32,2 micrograms/ml-1 (1 g) and 62,7 micrograms/ml-1 (2 g). The modelisation of the serum curves has been realized according to an open model with two compartments. A phase of rapid distribution is observed: t 1/2 alpha of 19.5 mn (1 g), 8.96 mn (2 g) followed by a phase of longer elimination: t 1/2 beta of 1.17 h (1 g), 1.15 h (2 g). The distribution volume at the steady-state is: 14.19 l (1 g), 14.76 l (2 g). This volume, much greater than the plasmatic volume, allows to suppose a good tissular diffusion of apalcilline. The urinary concentrations of the twelve first hours are: 182.64 micrograms/ml (1 g), 323 micrograms/ml (2 g). The urinary elimination during the 24 hours following the administration is: 18.58% (1 g), 16.47% (2 g).

Adult↗
PubMed1983

Cytotoxicity of cyclodepsipeptides on murine lymphocytes and on L 1210 leukemia cells.

By in vitro experiments we have demonstrated an important cytotoxic effect of destruxins A, A2, B, B1 and E on L 1210 leukemia cells. This cytotoxic effect was measured by DNA synthesis. The cytotoxic effect on normal mouse spleen lymphocytes was also evaluated. For the most cytotoxic compound, destruxin E, 16 mg/kg was found to be the minimal dose necessary to kill all mice.

Animals↗
PubMed1982

[Is it preferable to prescribe 1 or 2 daily doses of sodium valproate?].

Enteric-coated tablets containing 1 500 mg of sodium valproate (VPA) were administered in a randomized fashion either once or three times a day for 7 days to 6 healthy adult volunteers. Plasma total VPA levels and unbound fractions of the drug were determined 2-hourly on the last day of each treatment. Peak plasma concentrations were higher, and minimum plasma concentrations lower with one single dose than with three doses. In subjects who received three doses, the concentration curves tended to plateau, with higher AUC values. However, none of the differences observed reached statistical significance. The clinical implications of these pharmacokinetic data are discussed.

Adult↗
PubMed1982

Liquid chromatography determination of clobazam and its major metabolite N-desmethylclobazam in human plasma.

A specific procedure for the analysis of clobazam and N-desmethylclobazam in plasma is described. Reversed-phase liquid chromatography was performed on a Radial-pak cartridge using a mixture of 45% acetonitrile and 55% buffer solution (pH 7); the ultraviolet detector was set at 254 nm. The method used diazepam as internal standard and diethylether as extraction solvent. The calibration curves are linear between 50 and 500 ng/ml for clobazam and between 100 and 1000 ng/ml for N-desmethylclobazam. The day-to-day precision of the procedure at clobazam plasma concentrations of 50, 250, and 500 ng/ml generated coefficients of variation of 2.2, 6.6, and 11.3%, respectively. No interference occurred in plasma from patients treated with various drugs. The method has been used to study the pharmacokinetics of clobazam and N-desmethylclobazam in patients receiving oral clobazam.

Adult↗
PubMed1982

[Forms of care, health evaluation at 10 months, and maternal behavior].

The purpose of this survey was the comparison of 4 forms of day care: day care center, baby minder, care at home by the mother herself or care at home by someone else. A sample of 1,010 children, born to French mothers in a public hospital in Paris, was examined at a check-up clinic organized by National Social Security for 10 months old children. Home care by the mother herself was more frequent for mothers with primary level education or for families with 2 children or more; care at home by someone else was often chosen by families with high social level. The health and psychosocial and motor development of the children were not very different according to the type of day care. There was a higher frequency of acute respiratory tract infections and a lower weight gain for children in day care centers. Mothers whose children went to a day care center were more anxious about medical symptoms and more often called for a doctor.

Body Weight↗
PubMed1980

Meal-dependent absorption of enteric-coated sodium valproate.

The effect of meals on valproic acid (VPA) absorption from an enteric coated (EC) formulation was investigated. In study I, six adult normal volunteers received a single 500 mg dose of sodium valproate in randomized treatments: fasting (A), with a meal (B) or 3 hours after a meal (C). There were significant differences between treatments in the latency period (Lp) defined as the time during which measured concentrations of VPA were less than 1 microgram/ml. Lp values for treatments A, B and C were: 1.67 +/- 1.25 hr, 6.75 +/- 3.98 hr and 7.63 +/- 3.15 hr respectively. In study II, six subjects (five from study I) received in a randomized fashion a 400 mg intravenous bolus dose of VPA and a 500 mg EC VPA tablet, 3 hours after a meal. The mean Lp value was 8.1 +/- 1.6 hr and the mean bioavailability was 100%. Clearance, volume of distribution and half-life values obtained after intravenous dosing were comparable to literature values. These results indicate that food intake delays but does not decrease the extent of absorption of VPA from an enteric coated formulation.

Adult↗
PubMed1977

Intestinal calcium-binding protein 3 months after massive small bowel resection in the piglet.

Changes in intestinal calcium-binding protein and calcium binding activity were studied at resection and 3 months after 90% small bowel resection in piglets and one adult pig. A calcium-binding protein (MW congruent to 11.000) with calcium-dependent eletrophoretic mobility was partially purified from mucosal extract of proximal jejunum, mid-gut, and ileum. The concentration of calcium-binding protein and the calcium-binding activity of the intact animals were found highest in the proximal jejunal segment, lowest in the ileal segment. After resection in the four surviving animals out of nine, a significant increase in calcium-binding activity was observed in the proximal jejunum and in the distal ileal segment. The change in calcium-binding activity was much more marked in the ileum than the jejunum. These data demonstrate that pig intestinal mucosa possesses an adaptive capacity to increase the synthesis of calcium-binding protein after massive small bowel resection.

Adaptation, Physiological↗
PubMedDate not supplied

Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug-resistant epilepsy.

Vigabatrin (GVG) (3 g/day) and placebo were compared as an add-on to standard therapy in therapy-resistant epileptic patients using a double-blind crossover design with randomized treatment allocation. Twenty-three patients entered the trial, with four dropping out due to either increased seizure frequency following the cross-over from GVG to placebo (n = 1), intolerance to GVG therapy (n = 2), or poor seizure record (n = 1). Of the 19 patients who completed the study, 17 had partial seizures, eight of whom had secondary generalization and two who had primary generalized seizures. Compared with placebo, GVG was associated with a significant reduction in seizure frequency (p less than 0.01), with 11 of 19 patients experiencing greater than 50% reduction in weekly seizure occurrence, two showing a 25-50% reduction, four unchanged, and two showing an increase in seizures. Global efficacy ratings were greater in the GVG period for 15 patients (p less than 0.05) compared with one in whom there was no period difference and two in whom ratings were higher in the placebo period. Fourteen of the 19 patients indicated a preference for the GVG period. Adverse effects observed during GVG treatment were generally mild and consisted of drowsiness, confusion, nausea, irritability, and constipation. No clinically significant alterations in laboratory test results were observed. No treatment-related changes in plasma concentrations of concomitant antiepileptic drugs were noted. These results confirm the antiepileptic efficacy of oral GVG in refractory epileptics.

Adolescent↗
PubMedDate not supplied

Eating seizures.

An 18-year old man had a cluster of three seizures in a few hours and then remained seizure-free without medication; his mother has experienced seizures induced by movement. A 29-year-old man has had recurrent seizures for six years. In both cases, seizures were partial motor seizures induced by chewing. They are considered to be a particular variety of movement-induced seizures triggered by proprioceptive afferents of muscular origin. This explanation does not account for the great majority of the 63 published cases of seizures precipitated by eating. Eating seizures represent a heterogeneous group of seizures with discrete electroclinical signs and mechanisms. The term "eating seizures" should be preferred to the term "eating epilepsy."

Adolescent↗
PubMedDate not supplied

Survey of seizure disorders in the French southwest. I. Incidence of epileptic syndromes.

An epidemiologic survey began on March 1, 1984, and ended on February 28, 1985. During this period, all neurologists and electroencephalographers of the department of Gironde, an administrative district of the French Southwest (1,128,164 residents in 1982) obtained information by questionnaire from all persons who had experienced an epileptic seizure for the first time in their lives. Recurrent, isolated, and situation-related seizures were included. Febrile convulsions and neonatal seizures were excluded. The global incidence rate of diagnosed epileptic seizures was 71.3/100,000. The incidence rates per year and per 100,000 persons by type of epileptic syndrome were 1.7 for idiopathic and 13.6 for symptomatic localization-related epilepsies, 5.6 for idiopathic and 1.1 for symptomatic generalized epilepsies, 1.9 for undermined epilepsies, 29.0 for situation-related seizures, 18.3 for isolated seizures, and 0.3 for television epilepsies. Other epileptic syndromes were not represented. Using a classification of epileptic syndromes and not of epileptic seizures reduces difficulties in an epidemiologic survey. Diagnosis of an epileptic syndrome is time dependent, however, and at follow-up some patients shift from one group to another.

Epilepsy↗