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Biomedical subjects

E Rey

Publications and source records attributed to E Rey.

At least 127 records · Page 7Linked to original sources
PubMed1989

[Use of the labelling of drugs with stable isotopes in clinical pharmacology in children].

There are only few studies available in the literature, using drugs labelled with stable isotopes in pediatric clinical pharmacology. However, the stable isotope methods are of great potential interest. These sensitive methods allow to quantitate drugs in small volumes of biological fluid with great specificity. They are innocuous and allow in vivo drug metabolic studies. Using 1-3 15N, 2 13C labelled theophylline, it has been possible to demonstrate N7-theophylline methylation into caffeine in premature neonates while this metabolic pathway is virtually not existent in adults. Stable isotope techniques allow to study intraindividual changes in kinetic parameters of drugs during maintenance therapy without discontinuing the drug. For instance, auto-induction of carbamazepine metabolism was demonstrated in children using stable isotope-labelled carbamazepine in serial pharmacokinetic studies during maintenance therapy. They also make bioavailability studies possible in children. These methods make possible new non invasive studies like CO2 breath test. Using 1-3-7 13C-caffeine we demonstrated the feasibility of the CO2 breath test in young infants and described the maturation of the N-demethylation pathway for caffeine. The correlation between the rate of 13C-CO2 elimination and caffeine plasma clearance indicates that the CO2 breath test is a non invasive method useful for measuring caffeine N-demethylation and that this test might theoretically be used for monitoring caffeine treatment.

Child↗
PubMed1988

Maturation of caffeine metabolic pathways in infancy.

The maturation of the different pathways of caffeine metabolism was studied during infancy. The group of children (n = 14) consisted of four premature newborn infants and 10 older infants who received caffeine citrate solution. Caffeine and 11 of its metabolites were measured by HPLC. Total demethylation and N3- and N7-demethylation increase exponentially with postnatal age; the plateau is reached by 120 days and accounts for 58.6%, 90.5%, and 79.3%, respectively. N1-demethylation shows no variation with postnatal age. It is suggested that N3-demethylation is more important in young infants than in adults and that maturation of N1-demethylation occurs later than 19 months of age. 8-Hydroxylation is mature as early as 1 month of age and may be higher in infants than in adults. Acetylation is not mature before at least 1 year of age. Differences in maturation rate of acetylation may be related in part to genetic acetylator status.

Acetylation↗
PubMed1988

Gentamicin monitoring in neonates.

The elimination of gentamicin (G) was studied in 103 neonates (30 premature) during the first month of life after 2.5 mg/kg i.v. (as infusion) over 20-30 min. G plasma levels, measured by EMIT assay, were obtained before and at 1, 2, 3, and 6 h after infusion. We derived individual first-order kinetic parameters and designed optimal dose regimens. G plasma clearance, half-life, and recommended dose (mg/kg/h) changed exponentially with postnatal age during the first 14 days of life. No significant changes in kinetic values were noted during the first 3 days of life; however, they varied linearly with gestational age when they were measured during this period. Apgar score at 10 min and blood urea nitrogen significantly influenced the same parameters. The predictive value of a designed dose regimen was evaluated at steady-state, after dosage adjustment using two plasma concentration values: the minimum plasma concentration was below 2 mg/L in 93% of the patients; the plasma concentration observed within 1 h after completion of the infusion was (mean +/- SD) 5.33 +/- 0.97 mg/L. Our data suggest that 2.5 mg/kg every 12 h is appropriate in most neonates except for 0-2-day-old premature infants who require 2.5 mg/kg every 18 h. Monitoring of G plasma levels is advisable in infants with low Apgar score and/or renal failure.

Age Factors↗
PubMed1988

Developmental changes of caffeine elimination in infancy.

Five neonates (4 premature) and 16 infants (6 prematurely born), 15-588 days old, received caffeine as citrate salt for apnea. Plasma samples were collected 0, 2, 4, 6 h after a dose and before the next scheduled one. Patients 8 and 9 were serially studied. Caffeine plasma concentrations were determined using HPLC. The caffeine elimination half-life and clearance varied linearly with gestational age and exponentially with postnatal age, the plateau being reached during the second trimester of life. Dose regimen guidelines as a function of postnatal age were derived from individually calculated doses and dosing intervals in order to achieve, at steady state, a caffeine mean plasma concentration of 11 mg/l with a minimum of 7.5 mg/l and a maximum of 14.5 mg/l. We suggest dosing intervals for infants before 1 month, 1-2 months, 2-4 months and after 4 months to be equal to 24, 12, 8 and 6 h, respectively. The individual recommended dose varies from 2 to 10 mg/kg (as caffeine base) making caffeine monitoring mandatory in infants.

Aging↗
PubMed1988

Maturation of caffeine N-demethylation in infancy: a study using the 13CO2 breath test.

Four premature neonates and eight infants 1-19 months old received caffeine for apnea. The usual morning oral dose was substituted by 1,3,7 13C-trimethylxanthine (13C-tri CAF) as the citrate salt. Five breath samples were collected the day before (day 1) and the day of 13C-tri CAF administration (day 2). Plasma (after each breath collection) and urine were collected on day 2. 13C-CO2 exhalation was determined by isotope ratio mass spectrometry. Caffeine and its metabolites were measured using high-pressure liquid chromatography. Assessment of the labeled CO2 in the breath revealed no detectable 13C-tri CAF N-demethylation activity in infants before 45 wk postconceptional age. However, demethylation (as urinary metabolites) has been detected before that age. Two-, 4-, and 6-h cumulative excretion of 13C-tri CAF as 13C-CO2 increased with postnatal age and correlated with caffeine plasma clearance (r = 0.840, p less than 0.01). These results were consistent with those obtained for urinary metabolites. In one infant (19 months old) the cumulative excretion of 13C-CO2 while crying was 65% of the value observed during quiet breathing. The measurement of caffeine demethylation using the caffeine CO2 breath test is feasible in infants and is a safe and noninvasive method to determine age related changes in P4501-dependent N-demethylase activity.

Apnea↗
PubMed1987

Effect of cimetidine on the pharmacokinetics of the new beta-blocker betaxolol.

The effect of cimetidine on the new beta-blocker betaxolol (Kerlone) was investigated in 7 healthy volunteers. Propranolol was used as a reference beta-blocking drug. In the control study, a single oral dose of propranolol (80 mg) was given (D0) followed by 5 daily doses of cimetidine (1 g) (D1-D6) and a second oral dose of propranolol (D7). The study was repeated with 20 mg of betaxolol replacing the propranolol dose. The oral clearance of propranolol was significantly decreased (21%). No significant effect of cimetidine on the kinetics of betaxolol was observed.

Adrenergic beta-Antagonists↗
PubMed1986

Sodium valproate monotherapy in childhood epilepsy.

154 patients with a mean age of 6 years 1 month were followed on valproate monotherapy for a period ranging from 5 to 27 months (mean 22 months). Absence epilepsies, benign myoclonic epilepsies and epilepsies with tonic-clonic seizures on awakening were the best controlled, followed by benign partial epilepsies and infantile spasms. Reduction to monotherapy resulted in improvement in 13 of 14 patients with primary generalized epilepsy. Sixteen per cent of the 154 patients suffered mild to moderate adverse effects. After cessation of treatment in 28 seizure-free patients, no recurrence was observed in absence epilepsy, benign myoclonic epilepsy, infantile spasms or benign partial epilepsy, whereas two thirds of the patients with generalized tonic-clonic seizures on awakening relapsed in the year following the cessation of the treatment.

Adolescent↗
PubMed1986

Effect of propranolol on alpha-amino-isobutyric acid and water kinetics in the materno-fetal unit of the rat.

Pregnant Sherman rats were given propranolol (a) per os (50 mg X kg-1, twice a day) on days 17-19 of gestation, (b) by constant rate infusion: osmotic minipumps (6 mg X kg-1 X day-1) from day 13 of gestation. On day 20 (a-treated) or 21 (b-treated), [14C]-AIB + [3H]-H2O were injected intravenously; plasma and tissue samples were collected at different times up to 4 h (a-treated) or at 2 h (b-treated) for radioactivity measurements. Whatever the treatment, no difference was found between control and treated animals for all parameters studied (number of fetuses; weight, protein; DNA; [14C]-AIB or [3H]-H2O tissue levels) except in propranolol-treated mothers where maternal heart [14C]-AIB uptake was decreased and where fetal plasma and tissue [3H]-H2O levels where higher than control at 5 min. Another set of experiments were performed in a-treated rats. On day 20, each mother was anesthetized with ether and injected as above; maternal plasma sample and one feto-placental unit were collected at different times within 15 min after injection. For this period, [14C]-AIB uptake and mainly [3H]-H2O diffusion were increased in placentae and fetuses of propranolol-treated dams. Arterial blood pressure did not change throughout the experiment in propranolol-treated animals, but decreased in controls. Heart rate was slowed down in the former compared to controls. Thus, in our experimental conditions, propranolol treatment: does not modify fetal weight; has no effect on AIB placental transfer and tissue uptake, and could protect towards the stress of anesthesia and surgical injuries, since H2O transfer was impaired in control but not in treated animals.

Aminoisobutyric Acids↗
PubMed1986

Buflomedil kinetics in patients with liver disease.

The pharmacokinetics of single intravenous (100 mg) and oral (450 mg) doses of buflomedil was studied in 3 and 6 patients respectively, suffering from chronic liver disease. Comparisons of buflomedil kinetic parameters between the patients and healthy subjects indicate a significant increase in AUC0 infinity, T beta, u' and a significant decrease in Cle', Clnr when the patients received the oral dose, but no significant differences when the patients received the intravenous dose probably due to the small number of patients explored. The elimination of buflomedil is impaired in chronic hepatic disease. It seems advisable to reduce the usual dose to half its value when the prothrombin index is around 50% associated with a low albumin concentration and a low factor V.

Administration, Oral↗
PubMed1986

[Study of peripheral resistance in pregnant women. Preliminary results].

Variations in blood pressure (BP), heart rate (HR) and peripheral arterial blood flow (BF) were measured during the "roll-over" test (ROV) by impedance plethysmography. With these parameters, the peripheral vascular resistance (PR) was estimated in 17 normotensive and 8 hypertensive women between 28 and 32 weeks of pregnancy. In the normotensive women, a mean drop of 10.97% in BF and mean increase of 49.85% in PR were observed. Chronic hypertensive women with good evolution during pregnancy had a 96.30% (p less than 0.01) drop in their BF and a 399.38% (p less than 0.01) increase in their mean PR. Changes in BF and PR in chronic hypertensive women with obstetrical complications were similar to the normotensive women: BF increased by 4.50% and PR decreased by 0.04%. The increase in PR in the normotensive group could be due to a release of circulating vasopressive agents. In the chronic hypertensive group without complication this release could be more important or there might be an increase in the peripheral vascular sensitivity. In contrast, the lack of variation in PR in the chronic hypertensive group with obstetrical complications could be due to already established arterial vasospasm.

Blood Flow Velocity↗