Biomedical subjects

E Rey

Publications and source records attributed to E Rey.

At least 91 records · Page 5Linked to original sources

PubMed1995

Pharmacokinetics of cetirizine in 2- to 6-year-old children.

Eight children (3.84 +/- 1.17 years old) received a single oral 5 mg cetirizine dose (0.32 +/- 0.07 mg.kg-1) as a 10 mg.ml-1 solution, 1.73 (+/- 0.64) hours before a minor surgical intervention (mean duration +/- SD = 0.90 +/- 0.25 h). Seven venous blood samples were collected before administration (t0) and 0.5 h, 1.5 h, 4 h, 8 h, 12 h and 24 h after dosing, and urine samples were collected up to 24 hours after the dose. The mean +/- SD kinetic parameters were: peak plasma level (Cmax) 607 +/- 231 micrograms.l-1 reached in 1.93 +/- 1.39 h (tmax), elimination half-life (t1/2) 5.55 +/- 0.98 h, area under the plasma concentration time curve (AUC0-infinity) 4,772.1 +/- 1,318.4 micrograms.l-1.h, mean residence time (MRT) 8.13 +/- 1.31 h, apparent plasma clearance (Cl/f) 1.27 +/- 0.80 ml.min-1.kg-1, apparent volume of distribution (Vz/f) 0.60 +/- 0.38 l.kg-1. Urinary recovery was 38.4 +/- 9.9% (n = 4) of the dose. Renal clearance was 0.42 +/- 0.10 ml.min-1.kg-1 (n = 6). No influence of age on the cetirizine parameters was evidenced among this group, except for MRT (p < 0.05) which decreases with age. When compared with results in adults, elimination half-life (t1/2) was twice as short and apparent clearance twice as great. These results suggest that a higher dosage b.i.d. may be required in children.

Administration, Oral↗

PubMed1994

Sleep EEG of patients with obsessive-compulsive disorder.

Twenty-two patients suffering from an obsessive and compulsive disorder (OCD) according to DSM-III-R were investigated by polysomnographic sleep EEG recordings under drug-free conditions and compared to age- and sex-matched healthy controls. Sleep efficiency was significantly lower and wake % SPT was significantly increased in the patient group compared to healthy subjects. Sleep architecture did not differ among the two samples. Especially REM sleep measures, in particular, REM latency did not differ among the groups. No positive correlation was found between sleep variables and rating inventories for obsession and compulsions (Y-BOCS), depression (Hamilton) and anxiety (CAS). A secondary depression did not influence sleep EEG variables. The results of this study contradict the assumption that OCD patients show REM sleep and slow wave sleep abnormalities similar to those shown by patients with primary depression.

Adult↗

PubMed1994

Epidural anaesthesia for elective caesarean section does not influence fetal umbilical artery blood flow indices.

This prospective study was completed to determine the influence of epidural anaesthesia on the fetoplacental circulation of normal subjects. Thirty-seven normal pregnant patients at term, undergoing elective Caesarean section, had Doppler measurements of the fetal umbilical artery blood flow velocity before and after epidural anaesthesia using lidocaine 2% without epinephrine. There were no differences in systolic/diastolic, resistance or pulsality indices following epidural anaesthesia. These results suggest that this technique has no adverse effect on fetoplacental circulation in normal non-labouring subjects.

Adult↗

PubMed1994

The prognosis of pregnancy in women with chronic hypertension.

OBJECTIVE: Our purpose was to assess pregnancy outcomes in women with chronic hypertension from a population with a perinatal mortality of 12 in 1000. STUDY DESIGN: A longitudinal cohort study was performed between 1987 and 1991 in Montreal, Quebec, Canada. RESULTS: A total of 337 pregnancies in 298 women with chronic hypertension were followed up. The following outcomes were statistically more frequent in the hypertensive women than in the general population (p < 0.01): perinatal mortality (45/1000 vs 12/1000), preeclampsia (21.2% vs 2.3%), premature delivery (34.4% vs 15.0%), small-for-gestational-age newborns (15.5% vs 6.3%), primary cesarean sections (29.6% vs 14.2%), and gestational diabetes (33.1% vs 12.0%). Preeclampsia was associated with prematurity, small-for-gestational-age newborns, cesarean section, and neonatal complications. Even without superimposed preeclampsia hypertensive women had significantly higher frequencies of perinatal death (29/1000) and small-for-gestational-age newborns (10.5%) than did normotensive women (p < 0.05). CONCLUSIONS: In our population women with chronic hypertension with or without superimposed preeclampsia, have a higher incidence of perinatal death and small-for-gestational-age newborns than the general population does.

Adult↗

PubMed1994

Safety, tolerability, efficacy and plasma concentrations of tropisetron after administration at five dose levels to children receiving cancer chemotherapy.

In a double-blind, placebo-controlled, escalating dose study, 44 children receiving cancer chemotherapy of various degrees of emetogenicity were randomly allocated to once-daily treatment with tropisetron 0.05 mg/kg (6 patients), 0.10 mg/kg (5 patients), 0.20 mg/kg (6 patients), 0.33 mg/kg (6 patients), 0.50 mg/kg (6 patients) or placebo (15 patients). All doses of tropisetron were well tolerated; no tropisetron recipient discontinued treatment because of intolerance and no adverse effect could be plausibly correlated to tropisetron administration. Therapeutic plasma concentrations of tropisetron (> 3 ng/ml) were present for 9 h after administration of doses of 0.10 mg/kg or more. Tropisetron at doses of at least 0.20 mg/kg was significantly more effective in preventing vomiting than lower tropisetron doses or placebo, both in terms of treatment failure (> four vomits) (P = 0.015) and patient and investigator efficacy ratings (P = 0.04 for investigator rating; P = 0.035 for patient rating). Further comparative studies of the efficacy of tropisetron in chemotherapy-induced emesis in children are warranted.

Adolescent↗

PubMed1994

Stereoselective disposition of ibuprofen enantiomers in infants.

The pharmacokinetics of the enantiomers of ibuprofen were investigated after oral administration of a single 7.6 +/- 0.3 mg kg-1 dose of the racemate in 11 infants. Mean (+/- s.d.) half-lives were 1.6 +/- 0.5 h for S(+) and 1.5 +/- 0.5 h for R(-) and mean (+/- s.d.) AUC values were 31.5 +/- 14.3 mg l-1 h for S(+) and 36.6 +/- 13.8 mg l-1 h for R(-). Since plasma concentrations of the active S(+)-isomer were lower than those reported in adults, a higher dosage might be required in infants.

Administration, Oral↗

PubMed1994

Biotransformation of caffeine in human liver microsomes from foetuses, neonates, infants and adults.

1. Caffeine metabolism was studied in human liver microsomes from foetuses (n = 10), neonates (n = 10), infants (n = 9) and adults (n = 5). Caffeine and its metabolites, 1-3-7-trimethyluric acid, paraxanthine, theophylline and theobromine, were assayed by h.p.l.c. Methoxyresorufin-O-demethylase activity (MEROD) was determined and immunoquantifiable levels of CYP1A2 were measured. 2. The formation of the dimethylxanthines by N-3, N-7 or N-1-demethylation was significantly less in foetuses, neonates and infants than in adults, as shown previously in vivo. The formation of 1-3-7-trimethyluric acid (C-8-hydroxylation) was not significantly different between age groups. The production of total dimethylxanthines, paraxanthine and theophylline increased significantly with age within the neonate-infant group over at least the 0-300 day range (rs = 0.739, 0.667, 0.682, respectively). These data differ from those reported in vivo which suggested that N-3 and N-7-demethylations matured at about 120 days. The difference in maturational profiles of each metabolic pathway suggests that the reactions depend on different isoenzymes. The delay in the maturation of N-1 compared with N-3 and N-7-demethylation is in agreement with previous in vivo data. 3. In the neonate-infant group, only N-3-demethylation correlated with both MEROD activity (rs = 0.681; P < 0.05) and CYP1A2 microsomal concentration (rs = 0.454; P approximately 0.05), suggesting that, as in adults, this reaction depends on CYP1A2. 4. In the foetal samples, the production of total dimethylxanthines, paraxanthine and theobromine decreased significantly (rs = -0.879, -0.767, -0.708, respectively) with increasing gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Excretion of psychoactive drugs into breast milk. Pharmacokinetic principles and recommendations.

The postpartum period is a time of great physical and emotional changes. The incidence of psychiatric illness is higher in this period than at any other time in a women's life. Therefore, the question of whether women receiving psychotropic drugs should continue breast feeding is an important one. Drug excretion in breast milk depends mostly on passive diffusion of the unionised unbound drug. Passive diffusion is affected mainly by the drug disposition in lactating mothers, by the physicochemical properties of the molecule and by the protein and lipid contents of breast milk. Indeed, breast milk can be considered as a compartment with bidirectional transfer rather than a reservoir into which drug accumulates. Benzodiazepines are the most prescribed psychotropic drugs. Generally there does not seem to be any contraindication to breast feeding after a single dose, provided the dose administered is relatively low. If higher doses are to be used or long term administration is required, then breast feeding should probably be discontinued, particularly with drugs with a long elimination half-life. On the basis of the average concentration of phenobarbital (phenobarbitone) in milk, breast feeding is not recommended. For glutethimide, breast feeding would appear to be safe for the infant when a single dose is taken occasionally. Zopiclone may also be prescribed on a short term basis to breast feeding mothers. Due to limited available data or to the large amount transferred to milk, administration of phenothiazines and nonphenothiazine tricyclic, butyrophenone, and benzamide antipsychotics to breast feeding mothers cannot be recommended. Breast feeding is not always considered an absolute contraindication to lithium therapy, but the mother should watch for signs of toxicity in her baby. Whether clomipramine should be contraindicated during breast feeding depends on the concentration of active metabolites in breast milk, and this has not yet been determined. It is probably safe for mothers to breast feed while receiving amitriptyline, but before more conclusive recommendations are made more infants should be studied. The available data suggest that the amount of doxepin and its metabolite in breast milk is small. However, the metabolite of doxepin may accumulate in the infant with risk of sedation and respiratory depression: therefore, an alternative antidepressant should be selected for breast feeding mothers.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Anxiety Agents↗

PubMed1994

[Pharmacokinetics of diphemanil methylsulfate in infants].

BACKGROUND: Diphemanil methylsulfate is an atropin-like drug used in some infants suffering from vagal bradycardia. Its pharmacokinetic parameters are known for adults but not for infants. The report describes these parameters in six infants. POPULATION AND METHODS: Five infants aged 35 to 109 days (mean: 62 +/- 28) and weighing 3.5 to 5.3 kg (mean: 4.3) were included in the study with the formal consent of their parents. All suffered from vagal hyperreactivity. The sixth younger full-term infant was aged 10 days and weighed 4 kg. They were given a single dose (3 mg/kg) of diphemanil methylsulfate orally, after a minimal fast of 4 hours. Blood samples were collected at T0 and 3, 6, 8, 12 and 24 hours after administration. Urines were also collected from 1 hour before drug administration to 24 hours after. Plasma concentrations of diphemanil methylsulfate were measured by gas-exchange chromatography. RESULTS: The peak plasma concentration in the five infants occurred at 3.9 +/- 2.3 hours (range: 2.9-8 hours). Half-life was 8.6 +/- 2.4 hours and tended to decrease with age. All the other parameters were identical to those found in adults. The peak plasma concentration occurred in the sixth younger infant at 2.9 hours, with a half-life of 17.2 hours. Renal clearance was high (0.3 l/h/kg). CONCLUSION: The relatively long half-life of diphemanil methylsulfate allows this drug to be given every 8 hours. This longer interval is more comfortable for the patients and their parents. The high renal clearance suggests that this drug is excreted by both glomerular filtration and tubular secretion.

Age Factors↗

PubMed1993

The organo-specific external NADH dehydrogenase of mammal heart mitochondria has an artefactual origin.

The existence of an organo-specific (heart) external NADH dehydrogenase located on the outer face of the inner mitochondrial membrane has been recently proposed. We have studied the respiration on external NADH in rat and beef heart mitochondrial fractions: (i) by using different mitochondrial isolation procedures on the rat, we observed that the higher the criteria of quality toward classical substrate respiration of mitochondrial fractions, the lower the external NADH-linked respiration; (ii) by using an especially loosely fitting glass-Teflon homogenizer, we obtained rat heart mitochondrial fractions practically free from external NADH linked respiration and with the highest respiratory control ratio on glutamate plus malate respiration. In rat and beef heart mitochondrial fractions containing an external NADH respiration: (i) ethoxyformic anhydride used previously to distinguish internal and external NADH oxidation was shown not to be specific; (ii) external NADH-linked respiration (although associated to the normally functioning respiratory chain as was shown by the effects of classic respiratory inhibitors) did not lead to ADP phosphorylation while glutamate plus malate did; (iii) respiratory activity on glutamate plus malate and external NADH was totally additive and the oxidation corresponded to two separate cytochrome oxidase pools, indicating a total functional separation between the two respiratory systems; (iv) NAD+ addition stimulated states 3 and 4 glutamate plus malate respiration to the same extent, indicating the presence of an appreciable number of internal dehydrogenases accessible to external cofactors. These results show that external NADH-linked dehydrogenase activity, which is usually detectable in mammal heart mitochondrial fractions, is of artefactual origin.

Animals↗

PubMed1993

Pharmacokinetics of diphemanil methylsulphate in infants.

The pharmacokinetics of diphemanil methylsulphate was evaluated after oral administration of a single 3 mg.kg-1 dose to 5 infants being treated for symptomatic bradycardia. The mean pharmacokinetic parameters of oral diphemanil methylsulphate in infants were similar to those in adults. The mean half-life was 8.6 h. This would allow administration three times a day in infants instead of four to six times a day, as currently prescribed. The mean residence time decreases significantly with age (Spearman's r' = -1), and there is a trend for the half-life to decrease with age (r' = -0.9; NS), suggesting an influence of maturation on its elimination.

Administration, Oral↗

PubMed1993

Dose-response study of metoclopramide in gastroesophageal reflux in infancy.

Twenty-four infants, 1 to 18 months-old, who were referred to four centers for suspected gastroesophageal reflux and whose esophageal pH after a standard formula meal given at 9 to 10 am (Ho-day 1) fulfilled the criterion of being < 4 for more than 5% of the time between H1 and H6, entered a double-blind placebo-controlled dose-response trial of metoclopramide (M). Twenty-four hours later (day 2), patients were randomly assigned to receive either placebo or a single 0.1, 0.2, or 0.4 mg/kg dose of metoclopramide, 30 min before the formula meal (n = 6/group) and the procedure was repeated. Metoclopramide plasma concentration was measured 1 h after dosing (C1h). On day 1, the time during which the esophageal pH was < 4 (time pH < 4), and five other parameters, were not significantly different in the treatment groups. On day 2, time pH < 4 (m(SD)) decreased from 33(13) to 30(33), 39(27), to 36(47), 42(15) to 18(13) and 48(25) to 31(46) min in the placebo, 0.1, 0.2, and 0.4 mg/kg metoclopramide groups, respectively. Possibly due to the large interindividual variability, no significant differences in parameters were observed between the different groups. None of the parameters correlated with the metoclopramide dose. Time pH < 4 expressed as the difference between day 1 and day 2, relative to day 1, decreased significantly as a function of C1h. No side effects were observed. A similar study should be performed after repeated dosing regimen.

Analysis of Variance↗

PubMed1993

Effect of age and disease on the pharmacokinetics of nimesulide.

Nimesulide is a nonsteroidal anti-inflammatory agent with additional antipyretic and analgesic activity. The recommended dosage is 100 to 200 mg twice daily orally or rectally. The pharmacokinetics profile of nimesulide has been studied in patients with a predisposition for altered pharmacokinetics. The pharmacokinetic profile of nimesulide and its hydroxy metabolite was not altered when the drug was administered in a standard regimen (100mg twice daily) to elderly patients aged < 80 years, suggesting that dosage adjustment is not necessary for such patients. In children aged 7 to 9 years, nimesulide 50mg administered in a granular formulation showed a tendency for greater absorption and elimination than that recorded for adults administered nimesulide in tablet form. These results suggest that the pharmacokinetic profile of this paediatric formulation should be assessed in children aged < 7 years to determine whether their dosage should be adjusted. In patients with moderate renal insufficiency, the pharmacokinetic profile of nimesulide was not altered even though the terminal elimination half-life of its hydroxy metabolite was greater and this resulted in slight accumulation with multiple dose administration in a standard regimen. This slight effect was not considered to be clinically significant and therefore dosage adjustment for patients with moderate renal impairment appears unnecessary. Administration of nimesulide to patients with severe renal failure should be avoided until the propensity and significance of hydroxy-nimesulide accumulation is quantified in this patient group. The pharmacokinetic profile of nimesulide has not been determined in patients with hepatic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1992

Pharmacokinetics of diphemanil methylsulphate in healthy subjects.

The pharmacokinetic parameters of oral diphemanil methylsulphate have been evaluated in six healthy male volunteers. Absorption of the drug was slow (tmax = 2 to 4 h), the mean half-life was 8.35 h, and the amount of the drug recovered in urine within 48 h ranged from 0.6 to 7.4% of the administered dose. The results suggest low bioavailability, assuming that the drug is poorly metabolized.

Administration, Oral↗

PubMed1992

Passage of S(+) and R(-) gamma-vinyl-GABA across the human isolated perfused placenta.

1. The maternal to foetal transfers of S(+)- and R(-)-gamma-vinyl-GABA (VGB) across the human isolated perfused placenta were low and comparable with those of acidic alpha-amino acids. 2. The placental uptake of the active S(+)-isomer from the maternal circulation exceeded that of the R(-)-isomer and this was reflected by a corresponding difference in placental tissue concentrations. 3. During perfusion with recirculation of the foetal medium, the two enantiomers were present at a similar concentration and did not concentrate in foetal perfusate, indicating that the excess amount of S(+)-VGB cleared from the maternal circulation was not accessible to the foetal perfusate. Furthermore, stable concentrations of both isomers in the foetal perfusate suggested a lack of placental metabolism. 4. Possible explanations of these findings include the operation of a stereoselective sodium-dependent-GABA placental uptake system on the maternal side, similar to that observed in neuronal tissue, or stereoselective binding to a placental GABA transaminase.

Aminocaproates↗

PubMed1992

Could saliva stand for plasma in theophylline monitoring in asthmatic children? Still a controversial problem.

Theophylline determination in saliva was proposed several years ago as a convenient and non-invasive alternative to monitoring plasma in children and adults. Published data demonstrated that theophylline saliva concentration linearly correlates plasma concentration. However, the variability found in interindividual serum/saliva ratios and the wide scattering among the data points precluded the clinical use of saliva for theophylline monitoring. The purpose of this study was to compare different standardized methods for obtaining stimulated saliva intending to reduce the variability in plasma/saliva ratios and to determine the most reliable one. A group of 150 ambulatory chronic asthmatic 4.5 to 20.83 (10 +/- 3.7; M +/- SD) year-old patients receiving theophylline 6.85 +/- 1.88 mg/kg every 12 h as slow release preparations for 4 to 100 days was studied. One ml venous blood and salivary specimens were simultaneously collected 5.15 +/- 0.36 h after the morning maintenance dose. In a subgroup of 75 patients, saliva was collected using first a new device called salivette, immediately followed by the collection of an expectorated sample 30 s after citric acid crystals stimulation. In the other patients saliva was collected using citric acid containing salivette. Theophylline concentration was determined using HPLC. For all types of saliva collection, salivary and plasma theophylline concentrations correlated significantly. However whichever method was used, based on the -2 to +2 SD interval, a large range of plasma theophylline was predicted from a single salivary theophylline concentration. Despite a further standardization of the sampling of saliva, saliva theophylline could not accurately predict plasma concentration.

Adult↗

PubMed1992

Activation of GABA B receptors in the anterior pituitary inhibits prolactin and luteinizing hormone secretion.

Previous work from our laboratory showed that baclofen could lower serum prolactin (PRL) levels acting at the central nervous system. The present experiments were designed to evaluate whether the gamma-aminobutyric acid B agonist was also effective in inhibiting hormone release at the pituitary level. In monolayer cultures of adenohypophyseal dispersed cells, baclofen inhibited basal PRL secretion after 1 or 2 h of incubation. This inhibition was significantly abolished by three antagonists: phaclofen, 3-aminopropyl-phosphonic acid and 4-aminobutylphosphonic acid. Furthermore, baclofen inhibited the thyrotropin-releasing hormone-induced PRL release in a concentration-dependent manner. With regard to gonadotropin secretion, baclofen was unable to modify basal luteinizing hormone (LH) secretion, but significantly inhibited the LH-releasing hormone-induced LH release. These results show that baclofen, in addition to its central neuroendocrine effects, inhibits pituitary hormone secretion, under basal and/or stimulated conditions, by direct action at the pituitary level.

Animals↗

PubMed1992

Vigabatrin. Clinical pharmacokinetics.

Vigabatrin is a structural analogue of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). It is supplied as a racemic mixture, with the S(+) enantiomer possessing pharmacological activity. [R,S]-Vigabatrin plasma concentrations can be estimated using high-performance liquid chromatographic methods. Only gas chromatography-mass spectrometry methods allow quantification of the S(+) and R(-) enantiomers. Vigabatrin was rapidly absorbed reaching peak concentrations within 1 to 2h. Area under plasma concentration-time curves indicated dose-linear pharmacokinetics. There was no effect of food on the absorption of vigabatrin. The absorption characteristics of the enantiomers were similar to those of the [R,S]-vigabatrin. No chiral inversion was detected after administration of the pure S(+) enantiomer. Vigabatrin is not protein bound. The apparent volume of distribution of [R,S]-vigabatrin was approximately 0.8 L/kg. Despite the lack of protein binding, cerebrospinal concentrations of the [R,S]-vigabatrin were only 10% of the plasma concentration 6h after a single oral dose. The half-life of [R,S]-vigabatrin was between 5.3 and 7.4h, the half-life of the enantiomers were 7.5 and 8.1h for the S(+) and the R(-) forms, respectively. The major route of elimination was renal excretion; urinary recovery of the [R,S]-vigabatrin was close to 70%. Pharmacokinetic studies in epileptic children did not show any significant effect of maturation on the disposition of the S(+) enantiomer: the half-life and the renal clearance were similar to adult values. Data suggest a lower bioavailability in children. In adults with epilepsy, the half-life of the [R,S]-vigabatrin ranged from 4.2 and 5.6h, similar to that measured in healthy adults. In elderly nonepileptic volunteers the pharmacokinetics of the enantiomers of vigabatrin showed delayed absorption, a major increase in peak concentration and a prolonged half-life. These changes were attributed to decreased renal clearance of vigabatrin. A nonlinear relationship between renal clearance and creatinine clearance was suggested. Vigabatrin caused a 20% fall in plasma phenytoin concentrations, the mechanism of which has not been elucidated. There were no other interactions with most concurrently administered anticonvulsants. The usual dosage of vigabatrin as add-on treatment in adults is 2 to 4g daily. Higher dosages up to 80 mg/kg daily were required in children. A dosage adjustment was recommended in any patient with decreased renal clearance. Although anticonvulsant effects were clearly related to dosage, monitoring of plasma concentrations of vigabatrin as a guide to dosage is unlikely to be of as much value as with other antiepileptic drugs. The action of the drug long outlasts its presence in plasma.

Administration, Oral↗