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Biomedical subjects

E Rey

Publications and source records attributed to E Rey.

At least 73 records · Page 4Linked to original sources
PubMed1997

Report of the Canadian Hypertension Society Consensus Conference: 2. Nonpharmacologic management and prevention of hypertensive disorders in pregnancy.

OBJECTIVE: To provide Canadian physicians with comprehensive, evidence-based guidelines for the nonpharmacologic management and prevention of gestational hypertension and pre-existing hypertension during pregnancy. OPTIONS: Lifestyle modifications, dietary or nutrient interventions, plasma volume expansion and use of prostaglandin precursors or inhibitors. OUTCOMES: In gestational hypertension, prevention of complications and death related to either its occurrence (primary or secondary prevention) or its severity (tertiary prevention). In pre-existing hypertension, prevention of superimposed gestational hypertension and intrauterine growth retardation. EVIDENCE: Articles retrieved from the pregnancy and childbirth module of the Cochrane Database of Systematic Reviews; pertinent articles published from 1966 to 1996, retrieved through a MEDLINE search; and review of original randomized trials from 1942 to 1996. If evidence was unavailable, consensus was reached by the members of the consensus panel set up by the Canadian Hypertension Society. VALUES: High priority was given to prevention of adverse maternal and neonatal outcomes in pregnancies with established hypertension and in those at high risk of gestational hypertension through the provision of effective nonpharmacologic management. BENEFITS, HARMS AND COSTS: Reduction in rate of long-term hospital admissions among women with gestational hypertension, with establishment of safe home-care blood pressure monitoring and appropriate rest. Targeting prophylactic interventions in selected high-risk groups may avoid ineffective use in the general population. Cost was not considered. RECOMMENDATION: Nonpharmacologic management should be considered for pregnant women with a systolic blood pressure of 140-150 mm Hg or a diastolic pressure of 90-99 mm Hg, or both, measured in a clinical setting. A short-term hospital stay may be required for diagnosis and for ruling out severe gestational hypertension (preeclampsia). In the latter case, the only effective treatment is delivery. Palliative management, dependent on blood pressure, gestational age and presence of associated maternal and fetal risk factors, includes close supervision, limitation of activities and some bed rest. A normal diet without salt restriction is advised. Promising preventive interventions that may reduce the incidence of gestational hypertension, especially with proteinuria, include calcium supplementation (2 g/d), fish oil supplementation and low-dose acetylsalicylic acid therapy, particularly in women at high risk for early-onset gestational hypertension. Pre-existing hypertension should be managed the same way as before pregnancy. However, additional concerns are the effects on fetal well-being and the worsening of hypertension during the second half of pregnancy. There is, as yet, no treatment that will prevent exacerbation of the condition. VALIDATION: The guidelines share the principles in consensus reports from the US and Australia on the nonpharmacologic management of hypertension in pregnancy.

Female↗
PubMed1997

Influence of stiripentol on cytochrome P450-mediated metabolic pathways in humans: in vitro and in vivo comparison and calculation of in vivo inhibition constants.

OBJECTIVE: The spectrum of cytochrome P450 inhibition of stiripentol, a new anticonvulsant, was characterized in vitro and in vivo. METHODS: Stiripentol was incubated in vitro with (R)-warfarin, coumarin, (S)-warfarin, (S)-mephenytoin, bufuralol, p-nitrophenol, and carbamazepine as probes for CYPs 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4, respectively. Caffeine demethylation and the 6 beta-hydroxycortisol/cortisol ratio were monitored in vivo before and after 14 days of treatment with stiripentol as measures of CYP1A2 and CYP3A4 activity, and dextromethorphan O- and N-demethylation were used to measure CYP2D6 and CYP3A4 activity, respectively. In vivo inhibition constants for CYP3A4 were calculated with use of data that previously documented the interaction between stripentol and carbamazepine. RESULTS: In vitro, stiripentol inhibited CYPs 1A2, 2C9, 2C19, 2D6, and 3A4, with inhibition constant values at or slightly higher than therapeutic (total) concentrations of stiripentol, but it did not inhibit CYPs 2A6 and 2E1 even at tenfold therapeutic concentrations. In vivo inhibition of caffeine demethylation and dextromethorphan N-demethylation were consistent with inhibition of CYP1A2 and CYP3A4, respectively. The 6 beta-hydroxycortisol/cortisol ratio did not provide a reliable index of CYP3A4 inhibition. Inhibition of CYP2D6-mediated O-demethylation was not observed in vivo. With use of carbamazepine, in vivo inhibition constants for CYP3A4 ranged between 12 and 35 mumol/L, whereas the corresponding in vitro value was 80 mumol/L. CONCLUSIONS: Stiripentol appears to inhibit several CYP450 enzymes in vitro and in vivo. In vivo inhibition constants show that stiripentol inhibition of CYP3A4 is linearly related to plasma concentration in patients with epilepsy.

Adult↗
PubMed1997

Isoniazid acetylation metabolic ratio during maturation in children.

Isoniazid acetylation metabolic ratio (MR) was studied in 61 children with tuberculosis after administration of isoniazid. MR was calculated as the molar acetylisoniazid to isoniazid concentration ratio. MR was used as a probe for N-acetyltransferase activity and to determine the acetylation phenotype. MR had a bimodal distribution with an antimode between 0.48 and 0.77. MR and the percentage of fast acetylators increased significantly with age. The cumulative frequency of fast acetylators increased with age, with a plateau reached around 4 years. MR value was checked during treatment in 44 children. All children but one who initially appeared as fast acetylators remained in this group after repeated testing. Among the 30 slow acetylators, 12 became fast acetylators, and 10 showed a variable phenotyping at different ages. A bimodal distribution of the isoniazid acetylation MR was shown in children, with an antimode close to that described in the literature and a maturation of isoniazid acetylation during the first 4 years.

Acetylation↗
PubMed1997

Usefulness of a breakfast test in the management of women with gestational diabetes.

OBJECTIVE: To assess the usefulness of a breakfast test in determining which women with gestational diabetes do not need self-monitoring of blood glucose levels (home monitoring). METHODS: A 1-hour post-standardized breakfast blood glucose below 7.8 mmol/L (140 mg/dL) was measured in 227 women and at or above 7.8 mmol/L in 115. Within each group, women were randomized to home monitoring with a meter or to clinic follow-up. Target glucose values were 5.3 mmol/L (95 mg/dL) fasting, 5.6 mmol/L (101 mg/dL) before meals, and 7.8 mmol/L (140 mg/dL) 1 hour postprandial. Up to these thresholds women on clinic follow-up were transferred to home monitoring. Insulin therapy was started on the same thresholds in women randomized or transferred to home monitoring. Large for gestational age (LGA) newborns represented the main outcome, with the transfer rate to home monitoring and need of insulin therapy the secondary ones. RESULTS: The LGA delivery rate was not significantly different in the two follow-up groups in women with a breakfast result below 7.8 mmol/L (9.8 versus 4.3%) but was higher in the clinic follow-up among women with a breakfast result at or above 7.8 mmol/L (13.3% versus 30.9%; P < .05). Fewer women with a breakfast result below 7.8 mmol/L were transferred to home monitoring (2.6 versus 52.7%; P < .001) or started on insulin therapy (3.6 versus 25.2%; P < .001). The breakfast test cutoff of 7.8 mmol/L predicted insulin need with a sensitivity of 91.0% and a specificity of 72.0% CONCLUSION: A breakfast test is useful in identifying a low-risk population in which clinic follow-up may be used safety.

Birth Weight↗
PubMed1997

Pharmacokinetics of the S(+) and R(-) enantiomers of vigabatrin during chronic dosing in a patient with renal failure.

AIMS: To study the pharmacokinetics of vigabatrin in a patient affected with tuberous sclerosis who developed major agitation and aggression, while receiving vigabatrin orally (1.5 g every 12 h) and in whom impaired renal function was diagnosed. METHODS: The patient received vigabatrin (0.5 g day(-1)). A pharmacokinetic study of the S(+) and R(-) enantiomers of vigabatrin was performed before and during dialysis. Plasma concentrations were measured at 0, 1, 2, 3, 4, 6, 12, 18 and 24 h by a specific GCMS assay. RESULTS: Before dialysis, the maximum and minimun plasma concentrations of vigabatrin at steady-state were lower for the S(+) than for the R(-) enantiomer, while the apparent oral clearance was higher for the S(+) than for the R(-) enantiomer (2.97 vs 0.48 l h(-1)). In addition, the haemodialysis clearance was similar for the two enantiomers (4.96 vs 5.15 l h(-1)). CONCLUSIONS: Vigabatrin is an irreversible inhibitor of GABA-transaminase, effective in the treatment of drug-resistant epilepsy and reported to be eliminated unchanged by renal excretion. Although vigabatrin is known to have stereoselective kinetics, the difference in plasma dry concentrations and pharmacokinetics of the S(+) and R(-) enantiomers that we observed during long term administration at high doses in a patient with impaired renal function, has not been reported before. The question remains of the potential toxicity of the high levels of the R(-) enantiomer.

Adult↗
PubMed1997

Preeclampsia and neonatal outcomes in chronic hypertension: comparison between white and black women.

We compared the incidence of preeclampsia and neonatal outcomes in 208 white (born in Canada) and 74 black (born in Haiti) women with mild chronic hypertension. Controls included 17,677 white and 2,400 black normotensive women delivered in the same center between 1987 and 1991. Superimposed preeclampsia (32.4% vs 14.9%; p < 0.01), perinatal mortality (9.5% vs 2.9%; p < 0.05) and prematurity (32.4% vs 19.7%; p < 0.05) were more frequent in black than in white women with chronic hypertension. Within both races, chronic hypertensive women with superimposed preeclampsia demonstrated higher rates of perinatal mortality and morbidity than controls. White chronic hypertensive women without preeclampsia and controls had similar rates of perinatal mortality as compared to black study participants and controls (2.3% vs 1.4%), small-for-gestational-age newborns (10.7% vs 7.8%) and prematurity (12.4% vs 15.3%). Compared to black controls, black chronic hypertensive women without preeclampsia had higher rates of perinatal mortality (1.2% vs 8.0%; p < 0.001) and prematurity (9.0% vs 18.0%; p < 0.05). These data provide evidence of ethnic differences in perinatal outcomes in chronic hypertensive women that are not explained only by superimposed preeclampsia.

Apgar Score↗
PubMed1997

Metoclopramide plasma concentration in neonates.

During the course of a multiple-dose metoclopramide (M) oral treatment, M plasma concentrations were measured just before (Cmin) and 1 hour after the administration (C1h) at steady-state in 5 (3 premature and 2 term) neonates. Mean Cmin was equal to 91.6 +/- 45.5 ng/ml and higher than C1h (87.4 +/- 43.2 ng/ml), but not significantly. A significant negative correlation was found between Cmin plasma concentration and gestational age as well as with postconceptional age, suggesting that the lower the gestational and postconceptional age, the lower the metoclopramide dosage should be.

Child↗
PubMed1996

Effect of stiripentol on carbamazepine plasma concentration and metabolism in epileptic children.

OBJECTIVE: To study the relationship between the plasma concentration of stiripentol (STP), a new antiepileptic drug, and its inhibitory effect on the formation of carbamazepine epoxide (CBZE) in epileptic children treated with carbamazepine (CBZ) either alone or in combination with another antiepileptic drug. METHODS: Minimum plasma concentration of antiepileptic drugs was measured before initiation of STP therapy (day 0) and on days 28 (STP 60 mg.kg-1.day-1) and 84 (STP 90 mg.kg-1.day-1) by HPLC. RESULTS: The CBZE/CBZ plasma concentration ratio decreased exponentially with increasing minimum plasma STP concentration (r = 0.80). The asymptote of the curve allowed the calculation of the minimum plasma STP concentration required to obtain the maximum inhibitory effect, i.e. 6.7 mg.l-1. CONCLUSION: The inhibitory effect of STP on CBZ metabolism expressed as the CBZE/CBZ plasma concentration ratio is dependent on STP plasma concentration, with a maximum effect at an average of 7 mg.l-1. The present data suggest that in order to evaluate the anticonvulsant efficacy of STP as add-on therapy, the minimum plasma STP concentration should be maintained above 7 mg.l-1 and the dosage of CBZ should simultaneously be decreased in steps by more than 50% to minimize the change in CBZ plasma concentration.

Adolescent↗
PubMed1996

Non invasive in vivo study of the maturation of CYP IIIA in neonates and infants.

OBJECTIVE: Cytochrome P450 III (CYP III) has previously been demonstrated in vitro in fetal liver. METHODS: A study was performed in 7 premature, 13 term neonates and 30 infants to assess whether or not maturation had any influence on CYP IIIA activity in children from birth to 1 year of age. A simple non invasive procedure was used (6 beta OHF/FF concentration ratio in a morning spot urine sample). RESULTS: The 6 beta OHF/FF ratio was 7.2, 7.9 and 5.0 in premature and term neonates and infants, respectively. CYP IIIA activity is present at birth, with a 6 beta OHF/FF ratio comparable to adults. Its activity seemed lower in infants. This might be due to the decrease in CYP IIIA7 activity during maturation after birth, which might be more rapid than the increase in CYP IIIA3/4 activity.

Age Factors↗
PubMed1996

Pharmacokinetics of the individual enantiomers of vigabatrin in neonates with uncontrolled seizures.

The antiepileptic drug vigabatrin (VGB) is a selective irreversible inhibitor of GABA-transaminase. It is administered as a racemic R(-), S(+) mixture, but the pharmacological activity of vigabatrin resides in the S(+) enantiomer and the R(-) enantiomer is inactive. The pharmacokinetic parameters of the two enantiomers have been studied after administration of a single oral 125 mg dose of the racemate to six neonates. The mean values of Cmax and AUC of the S(+) enantiomer were significantly lower (Cmax: 14.0 +/- 4.3 mg l-1; AUC: 143 +/- 44 mg l-1 h) than those of the R(-) enantiomer (Cmax: 34.1 +/- 9.5 mg l-1; AUC: 231 +/- 88 mg l-1 h), whereas no significant difference in the time to reach Cmax (S(+): 2.1 +/- 1.1 h; R(-): 2.2 +/- 1 h) was observed between the two enantiomers. During chronic administration (125 mg twice daily over 4 days), there was no evidence of accumulation of either enantiomer.

Anticonvulsants↗
PubMed1996

Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as add-on therapy in epileptic children.

1. Lamotrigine is a new antiepileptic drug, chemically unrelated to currently used antiepileptic medication. Its pharmacokinetics can be influenced by concomitant antiepileptic medication. 2. This study was performed to assess the pharmacokinetic profile of lamotrigine in three groups of children treated with different types of comedication: drugs known to induce, to inhibit or to have no clinically significant influence on drug metabolism, respectively. 3. Thirty-one children aged 6 months to 5 years were included and received a 2 mg kg-1 single oral dose. Lamotrigine plasma profiles were different between the three comedication groups. The half-lives (mean +/- s.d.) were: 7.7 +/- 1.8 h, 21.9 +/- 6.8 h, 44.7 +/- 10.2 h in the "inducer', "other' and "inhibitor' groups respectively. 4. Patients were then dosed to steady state, with the dosage adjusted on the basis of the single dose pharmacokinetics to achieve a minimum plasma concentration between 1.5 and 3 mg l-1. The mean minimum plasma concentration for the three groups was 2.54 +/- 1.28 mg l-1 at steady state. 5. Dosage of lamotrigine can be optimised with knowledge of the metabolic effects of antiepileptic comedication.

Anticonvulsants↗
PubMed1996

Dialysis clearance of buflomedil in hemodialysed patients.

Buflomedil (CAS 55837-25-7, Fonzylane) is a peripherally vasoactive drug which improves nutritional blood flow in ischaemic tissue of patients with peripheral vascular disease by the way of an increase of perfusion in the microcirculation. Ten hemodialysed patients with chronic renal failure treated with intravenous infusion of 400 mg of buflomedil during 4 h of dialysis were included in the first study. This study was carried out to determine the dialysis plasma clearance and the amount of drug dialysed during the first intravenous administration of buflomedil. The dialysis clearance calculated from the amount recovered in dialysate was (mean +/- SD) 25.4 +/- 25.6 ml/min. The drug recovery resulting from hemodialysis represented a small fraction of the dose (< or = 5%). A second study was carried out to determine the accumulation of buflomedil in chronic hemodialysed patient. The drug concentration were measured before and at the end (4 h) of the infusion of buflomedil in six other patients maintained on intermittent hemodialysis (3 per week) for 4 weeks. The average Cmin and Cmax were stable during the 12 successive dialyses (mean +/- SD intervals were between 0.36 +/- 0.53 and 0.66 +/- 0.79 microgram/ml for Cmin and between 5.15 +/- 2.19 and 7.37 +/- 1.76 micrograms/ml for Cmax), showing no trend of accumulation of buflomedil. These results agree with the pharmacokinetics of the drug which is mainly metabolised in the liver and has a low renal clearance. Dialysis is unable to modify significantly the plasma concentration of the drug in regularly dialysed patients.

Aged↗
PubMed1996

Pharmacokinetics of tiaprofenic acid in infants after a single oral dose.

Ten healthy infants (15.2 +/- 10.6 months old, range 6-35) anesthetized for minor surgery were given a single oral dose (3 mg x kg-1) of tiaprofenic acid (TA). Seven venous blood samples and 0-12 h urine were collected. TA concentrations in plasma and urine were measured by HPLC. Within the whole group the mean +/- SD kinetic parameters were: Cmax: 10.55 +/- 3.31 mg x l-1, Tmax: 1.73 +/- 0.87 h, AUC0-1 32.53 +/- 4.42 mg x l-1 x h, AUC0-infinity 35.33 +/- 4.73 mg x l-1 x h, t1/2 1.82 +/- 0.48 h, Cl/F: 0.09 +/- 0.01 l x h-1 x kg-1, VZ/F: 0.23 +/- 0.08 l x kg-1. Renal clearance was 0.030 +/- 0.009 l x h-1 x kg-1. 32% of the TA dose was recovered in urine, 60% of which was conjugated. AUC0-8h increased significantly with age. The TA kinetic parameters were close to those in 3 to 11-year-old children. The present study suggests slight differences in the TA kinetics between infants and adults. However, the lack of an evidenced direct relationship between plasma TA concentration and either efficacy or tolerance suggests that the TA dose regimen in infants may not have to be different from that in adults.

Administration, Oral↗
PubMed1996

Carbohydrate intolerance in pregnancy: incidence and neonatal outcomes.

OBJECTIVE: To determine the incidence of carbohydrate intolerance during pregnancy and its impact on neonatal outcomes, which have not been formally established in Canada. DESIGN: Chart review. PARTICIPANTS: All 1432 women who delivered a single newborn in the months of May and September 1992 in Hôpital Sainte-Justine, Montreal, Hôpital Maisonneuve-Rosemont, Montreal, and Centre hospitalier de Rouyn-Noranda, Rouyn, Que. Women with multiple births or pre-existing diabetes mellitus were excluded. OUTCOME MEASURES: Carbohydrate intolerance, including gestational glucose intolerance (one abnormal result of an oral glucose tolerance test) and gestational diabetes mellitus (two or more abnormal results of the test); neonatal outcomes, including birth weight, hypoglycemia and hyperbilirubinemia. RESULTS: Of the 1074 women tested, 72 (6.7%) had gestational glucose intolerance and 98 (9.1%) had gestational diabetes mellitus. Of those women with carbohydrate intolerance, 120 were treated and 50 were not. Women who were not treated had higher rates of poor neonatal outcomes than women without carbohydrate intolerance (p < 0.05) or than women with carbohydrate intolerance who had received treatment (p < 0.05). Women who were not treated had higher rates of newborns with a birth weight of more than 4000 g (18.0%), large-for-gestational-age newborns (20.0%) and newborns with hypoglycemia (24.0%) or hyperbilirubinemia (40.0%) than women without carbohydrate intolerance (for whom the rates were 6.7%, 10.0%, 10.0% and 22.8%, respectively) or than women with carbohydrate intolerance who received treatment (for whom the rates were 6.7%, 6.7%, 10.0% and 21.7%, respectively). CONCLUSIONS: In this population, carbohydrate intolerance during pregnancy is a significant problem. Not only is the incidence rate higher than that usually estimated, but the impact on neonatal morbidity is also significant.

Adult↗
PubMed1995

Pharmacokinetic interaction studies between felbamate and vigabatrin.

To assess the possible occurrence of pharmacokinetic interactions between the antiepileptic agents felbamate and vigabatrin, two randomized, double-blind, placebo-controlled, crossover studies were conducted in healthy male volunteers. In Study I, 18 subjects received oral vigabatrin 1000 mg every 12 h for two 8 days periods with felbamate 1200 mg every 12 h or placebo. In Study II, 18 other volunteers were administered oral felbamate 1200 mg every 12 h for two 8 days periods with vigabatrin 1000 mg every 12 h or placebo. On the eighth day of each treatment period, blood and urine samples were collected over 12 h for determination of the active S(+)- and inactive R(-)-vigabatrin enantiomer concentrations (Study I) or felbamate concentrations (Study II). In Study I, the pharmacokinetic parameters of R(-)-vigabatrin were similar during co-administration with felbamate or placebo. Felbamate produced a 13% increase in AUC(0.12 h) and an 8% increase in urinary excretion of S(+)-vigabatrin. Although these changes were statistically significant, their magnitude was small. In Study II, the pharmacokinetic parameters of felbamate were similar during concurrent administration with vigabatrin or placebo. These data indicate that there are no clinically relevant pharmacokinetic interactions between felbamate and vigabatrin in man.

Administration, Oral↗