Biomedical subjects

E Rey

Publications and source records attributed to E Rey.

At least 109 records · Page 6Linked to original sources

PubMed1992

Effects of methyldopa on umbilical and placental artery blood flow velocity waveforms.

OBJECTIVE: To identify the effects of methyldopa on umbilical and placental artery Doppler velocity waveforms in mild preeclamptic and chronic hypertensive women with blood pressure below 160/110 mmHg. METHODS: Twenty-two normotensive, 11 untreated mild preeclamptic, 14 treated mild preeclamptic, 29 untreated chronic hypertensive, and 14 treated chronic hypertensive women were studied. Methyldopa was begun if the blood pressure remained higher than 140/90 mmHg after 24 hours of hospitalization. The pulsatility index (PI) was measured on days 0 and 7. RESULTS: Blood pressure decreased significantly with methyldopa in chronic hypertensive women only (P < .05). The PI did not vary in the umbilical artery in the five groups, or in the placental artery in normotensive, untreated preeclamptic, and untreated chronic hypertensive women. The PI decreased significantly in treated preeclamptic and chronic hypertensive women (P < .05). Birth weight was similar in the hypertensive groups. CONCLUSION: Methyldopa decreases placental vascular resistance in mild preeclamptic and chronic hypertensive women.

Adult↗

PubMed1992

[Pharmacokinetics and pharmacodynamics of a new 80 mg oral delayed-action isosorbide dinitrate preparation].

A new galenic form of isosorbide dinitrate (consisting of a hydrophilic matrix which allows very slow release of the active drug) was studied from the pharmacokinetic and pharmacodynamic view points in 11 patients with stable angina pectoris under betablocker therapy. After testing their sensitivity to nitrates with a sublingual trinitrin test causing a fall greater than or equal to 20 mmHg in systolic and greater than or equal to 10 mmHg in diastolic blood pressure, the patients were given a single tablet of Risordan LP 80 daily for 7 days. The equilibrium plasma concentrations of isosorbide dinitrate and its mononitrate metabolites (2-isosorbide mononitrate and 5-isosorbide mononitrate) over 24 hours were measured on the 6th treatment day. A method of measuring these nitrate derivatives has been developed and validated. The concentrations measured enabled the study of the pharmacokinetics of this new form, showing an average minimal concentration of 5-isosorbide mononitrate (principal metabolite) of 85 +/- 41 micrograms/l and an amplitude of fluctuation over the 24 hours period of 296 +/- 102 micrograms/l. From the pharmacodynamic point of view, the evaluation of the sensitivity to a single dose of 0.75 mg of trinitrin 24 hours after the first dose of Risordan LP 80, just before the second dose and 24 hours after the seventh dose, showed a significant difference (average decrease of 40 +/- 19 mmHg in systolic blood pressure) with respect to the values observed during the selection phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration.

Twelve children 1-5 y old were randomly assigned to receive midazolam 0.2 mg.kg-1 either by the intravenous (IV) or intranasal (IN) routes. After IN administration the rapid onset of absorption was observed (tmax 12 min). After both routes of administration the half-life was similar (2.2 h IN and 2.4 h IV). After IN administration the apparent plasma clearance and volume of distribution were about twice as high as after IV administration. The results are consistent with an estimated mean bioavailability of 55%.

Administration, Intranasal↗

PubMed1991

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

Twelve healthy children in three age groups anaesthetized for minor surgery were given a single oral dose of tiaprofenic acid (3 mg.kg-1) (TA). Seven blood samples and zero to 8 and 8 to 24 h urines were collected. TA concentrations in plasma and urine were measured by HPLC. No significant difference was found between the age groups in the kinetic parameters of TA and no correlation was found between these parameters and age: tmax = 2.12 h, Cmax = 8.78 mg.l-1, AUC(0----8 h) 33.9 mg.h.l-1, AUC = 39.3 mg.h.l-1, t1/2 = 2.35 h, Vt = 0.319 l.kg-1, CL = 0.094 l.h-1.kg-1. Renal clearance was 14 ml.h-1.kg-1.33% of the TA dose was recovered in the 24 h urine, 48% of which was conjugated, whereas in adults, TA is only found in urine as conjugates. The apparent plasma clearance was significantly higher (56%) than in 12 healthy adults given 1.5 mg.kg-1 TA. Volume of distribution and t1/2 did not significantly differ between children and adults. Since no relationship has been established between plasma TA and either efficacy or toxicity, a different dose regimen cannot be recommended in 3-11 year-old children from that in adults.

Administration, Oral↗

PubMed1991

Caffeine acetylator phenotyping during maturation in infants.

Caffeine acetylator phenotype was studied during maturation in 54 8- to 447-d-old children hospitalized for minor disease (group A) and in five 3- to 630-d-old children with Pierre Robin syndrome (group B). In group A, the children received 2.5 mg/kg caffeine orally once between birth and 15 mo. Group B patients were chronically treated with caffeine (2.3 to 15.8 mg/kg/d) for prevention of apneas, and the acetylator phenotype was serially determined. Phenotyping was performed on a spot urine sample collected 2-6 h after drug administration. Caffeine metabolites [5-acetylamino-6-formylamino-3-methyl uracil (AFMU), 1-methylxanthine, 1-methyluric acid, 1,7-methyluric acid, and 1,7-methylxanthine] were measured using HPLC. Acetylator phenotype was determined on the basis of AFMU/1-methylxanthine (ratio 1) and AFMU/AFMU + 1,7-methyluric acid + 1-methylxanthine + 1,7- methylxanthine + 1,7-methyluric acid (ratio 2) molar ratios. In group A, all children were slow acetylators before 83 d of age (ratio 1 less than 0.4; ratio 2 less than 0.08), whereas older children included slow and fast acetylators. The acetylation molar ratios differed significantly between age groups and increased with age. The cumulative percentage of fast acetylators increased with age but the plateau was not yet reached at 15 mo. In three children, the phenotyping was repeated after 15 mo: the second determination was consistent with the first one. In group B, all children appeared as slow acetylators on the first phenotyping. Four of them appeared subsequently as fast acetylators; one remained a slow acetylator until 11 mo.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗

PubMed1991

Further evidence for the inhibitory action of baclofen on a prolactin-releasing factor.

The mechanism of action of a specific gamma-aminobutyric acid B receptor agonist, beta-p-chlorophenyl-gamma-aminobutyric acid or baclofen, in its inhibitory action on prolactin release, was studied. Dose-response studies of the effect of baclofen on prolactin (PRL) secretion were performed in stressed male rats. Furthermore, the action of the drug was evaluated in (i) rats treated with haloperidol or alpha-methyl-p-tyrosine, (ii) stressed or suckled rats pretreated with sulpiride, and (iii) animals treated with serotonin, alone, or with alpha-methyl-p-tyrosine. Baclofen showed a clear dose-dependent inhibition of prolactin secretion in males under stress. The drug was unable to inhibit the prolactin release induced by haloperidol or alpha-methyl-p-tyrosine, although it reduced the PRL secretion induced by serotonin. It also inhibited PRL release in sulpiride-pretreated stressed or suckled rats. These results suggest that the dose-dependent effect of baclofen on PRL secretion is the consequence of an inhibition exerted on the prolactin-releasing factor component of the neuroendocrine responses evoked by stress or suckling, possibly acting at the serotonergic system.

Animals↗

PubMed1991

A simple non-invasive procedure for the investigation of cytochrome P-450 IIIA dependent enzymes in humans.

Urinary 6 beta-hydroxycortisol (6 beta OHF) is a specific marker of the induction of the cytochrome P-450 IIIA. Often, the production of 6 beta OHF is expressed from 24-h urine collection as the ratio 6 beta OHF/17-hydroxycorticosteroids or even better 6 beta OHF/free cortisol in order to adjust for minor day to day variation in adrenal cortisol production. A 24-h urine collection is a non-invasive method applicable to clinical studies in adult man, but more difficult to realize in newborn and infants. Therefore, we have tested the validity of a single urine sampling for the determination of the 6 beta OHF/free cortisol ratio as a clinical test to estimate cytochrome P-450 IIIA enzyme activity. Urinary 6 beta OHF and free cortisol have been measured in 19 healthy volunteers by high performance liquid chromatography methods using the same extraction procedure. A good correlation was found between 6 beta OHF/free cortisol ratio in morning urine samples and in 24h-collections (r = 0.899). Thus, a morning spot urine sampling is a simple procedure that may be helpful for investigations on cytochrome P-450 IIIA enzyme activity in humans, particularly in newborn and in children.

Adult↗

PubMed1990

[Transcutaneous transport of trinitrin in children after application of nitroglycerin patches].

Plasma levels of nitroglycerin were measured 13 to 24 hours after the application of nitroglycerin stamps in 7 children aged from 1 month to 7 years and suffering from heart failure. The plasma levels varied considerably from one patient to another, confirming that the bioavailability of transdermal nitroglycerin is extremely variable in children. Only 3 patients had a nitraemia higher than 1 ng/ml, a figure compatible with a haemodynamic effect of the drug. No side-effect associated with the nitroglycerin stamps was observed. The dosage we use (a quarter of a stamp for 5 kg bodyweight) seems to be adequate at the beginning of treatment, to be progressively increased according to the way the drug is tolerated.

Administration, Cutaneous↗

PubMed1990

Pharmacokinetics of oral cyclosporin A in diabetic children and adolescents.

Cyclosporin A (CsA) pharmacokinetics was studied in 19 diabetic children (mean age: 10.6 y). They were divided into prepubertal (I) and pubertal (II) groups according to plasma oestradiol or testosterone concentrations. The kinetic study was performed after a 72 h wash out period and a single oral dose of 7.5 mg/kg CsA. CsA in blood was measured by HPLC. The kinetic parameters: Cmax, tmax, t 1/2, AUC, CL/f, Vz/f and tss were calculated. No significant difference was found between the two groups. A significant negative correlation was found between Vz and both total cholesterol (r = -0.46), VLDL + LDL - cholesterol (r = -0.49) and VLDL + LDL - phospholipids (r = -0.58). CsA kinetics at steady-state were simulated by superimposition of single dose kinetics derived from each single dose. Measured steady-state blood concentrations were correlated (r = 0.80) with the values predicted by the simulation. The results suggest that CsA adjustment dosage of the CsA may be performed after a single oral dose using blood levels measured by HPLC. This procedure requires validation in further studies.

Administration, Oral↗

PubMed1990

The value of Doppler assessment of the uteroplacental circulation in predicting preeclampsia or intrauterine growth retardation.

Flow velocity waveforms of the uteroplacental arteries were analyzed at 20 and 24 weeks of gestation, by means of duplex pulsed Doppler ultrasonography, in 93 women at risk for preeclampsia or intrauterine growth retardation. The ability of an elevated resistance index to predict these conditions was tested. At 20 and 24 weeks an abnormal resistance index was significantly associated with intrauterine growth retardation but not with preeclampsia, with or without proteinuria. A low fetal abdominal circumference at 20 or 24 weeks or an increasing maternal plasma uric acid concentration at 24 weeks was as predictive as an elevated resistance index. In a second group of 43 women, screened in the same way, the only association was of an elevated resistance index at 20 weeks with intrauterine growth retardation. Although elevated resistance indices occur more commonly in women who develop intrauterine growth retardation and/or preeclampsia, the correlation is not close enough to be clinically useful as a screening test.

Blood Flow Velocity↗

PubMed1990

Intravenous lidocaine in the treatment of convulsions in the neonatal period: monitoring plasma levels.

Thirteen newborn infants (five premature, eight full term) with severe seizures and not responding to phenobarbital and diazepam received a lidocaine (LD) infusion. The schedule was 4 mg/kg/h on the 1st day, 3 mg/kg/h on the 2nd day, 2 mg/kg/h on the 3rd day, and 1 mg/kg/h on the 4th day. The LD plasma levels were measured every 24 h just before decreasing the dose. The control of seizures was achieved in 11 of 13 patients, with plasma LD concentration ranging from 2.8 to 10.5 mg/L. The LD concentration was linearly correlated with the dose in each group. In the premature group, LD clearance was always smaller than in the full-term group. Although no side effects were observed on heart rate and blood pressure, it is suggested that the dose of LD be adjusted to maintain the LD concentrations between 3-6 mg/L.

Diazepam↗

PubMed1990

Pharmacokinetics of the individual enantiomers of vigabatrin (gamma-vinyl GABA) in epileptic children.

1. The pharmacokinetics of the enantiomers of vigabatrin were investigated after oral administration of a single 50 mg kg-1 dose of the racemate to two groups of six epileptic children (I: 5 months-2 years, II: 4-14 years). 2. The mean (+/- s.d.) values of maximum plasma concentration and area under the plasma concentration-time curve of the R(-) enantiomer were significantly higher than those of S(+) vigabatrin in both groups: R(-) Cmax: 21 +/- 6.6 (I)-41.3 +/- 13.9 (II) vs S(+) Cmax: 13.9 +/- 4.5 (I)-23.8 +/- 12.2 (II) mg l-1; R(-) AUC: 106 +/- 28.5 (I)-147 +/- 34 (II) vs S(+) AUC: 90.9 +/- 27.9 (I)-117 +/- 26 (II) mg l-1 h. In group I, the half-life of the R(-) isomer was significantly shorter than that of the S(+) isomer; in group II, the half-lives were comparable. 3. For the R(-) enantiomer the area under the curve, and the elimination half-life increased linearly with age. 4. During chronic administration (50 mg kg-1 vigabatrin racemate twice a day for 4 days), the morning trough plasma drug concentrations did not increase.

Adolescent↗

PubMed1990

Effect of hypophysectomy on caffeine elimination in rats.

Two groups of 8-week-old Sprague-Dawley male rats were used: 8 hypophysectomized (H[-]), operated on day 0, treated by daily sc tetracosactid (ACTHs: 10 micrograms), and thyroxine (T4:5 micrograms/100 g); 7 sham-operated, treated by sc saline solution. ACTHs, T4, saline solution were administered on days 7-16. The animals received po caffeine (CAF) 4 mg/kg as citrate salt on day 15. Ten blood samples were drawn from the tail. Plasma CAF concentrations were determined by HPLC. CAF apparent clearance and apparent volume of distribution were lower in H(-) rats than in controls: 0.281 +/- 0.072 vs 0.455 +/- 0.165 l/kg/h (-38%; P less than 0.05) and 0.520 +/- 0.239 vs 1.28 +/- 0.266 l/kg (-59%; P less than 0.01) respectively. CAF half-life was lower in H(-) rats than in controls: 1.33 +/- 0.621 vs 2.12 +/- 0.676 h (-37%; P less than 0.01). CAF is a drug with a low hepatic extraction ratio and low plasma protein binding. CAF clearance is therefore primarily dependent on intrinsic clearance, which depends on the activity of the enzymes involved in CAF metabolism. These data suggest that hepatic CAF metabolism is reduced in H(-) rats treated by SC ACTHs and T4. The decrease in CAF apparent volume of distribution is probably related to dehydration, as suggested by increase in urine flow and hematocrit. The CAF half-life was probably low because the volume of distribution was proportionally more decreased than the clearance. Our results suggest that the pituitary gland plays a role in the regulation of hepatic CAF metabolizing enzymes.

Adrenocorticotropic Hormone↗

PubMed1990

[Macrosomia and maternal insulinemia in gestational diabetes].

Macrosomia is an important cause of neonatal morbidity. To detect the utility of plasma insulin level to predict neonatal macrosomia, we studied the glycemic and insulin responses to 100 g oral glucose tolerance test (OGTT) in 57 gestational diabetic women on diet therapy. Ten (17.5%) of them had macrosomic newborns. Macrosomia was defined as a birthweight higher than the 90th centile on our population scale. The mothers of the macrosomic newborns exhibited similar parity, body mass index, gestational age at OGTT and at delivery. Fasting capillary plasma glucose value was higher in women with macrosomic newborns (5.3 mmol/l +/- 0.4 vs 4.8 mmol/l +/- 0.4; p less than 0.01) as well as fasting capillary plasma insulin concentration (28.7 mU/L +/- 9.3 vs 17.7 mU/L +/- 6.4; p less than 0.01). The fasting glucose value was found to be more accurate than fasting insulin concentration to predict macrosomia (logistic regression and discriminant analysis). Thus, measuring insulin concentrations during an OGTT seemed to be unhelpful to predict macrosomia in gestational diabetic women.

Analysis of Variance↗

PubMed1990

Nitrofurantoin excretion in human milk.

Six lactating white healthy women (26-36 years old, weighing 45-58 kg) were treated with 50 mg nitrofurantoin tablets, a urinary antiseptic. They received either 50 mg (group I; n = 3) or 100 mg (group II; n = 3) 3 times a day (09.00, 16.00, 19.00 h) for 24 h, 2-5 days after the delivery of a full-term neonate. The study was performed on the 4th dose at 09.00 h just before breakfast. Milk samples were collected before, 3 and 6 h after the nitrofurantoin administration with an Egnell SMB breast pump. The complete milk samples were collected from each breast, and pooled. 5 ml venous blood samples were drawn before, 1, 2, 3 and 6 h after nitrofurantoin administration. Plasma and milk nitrofurantoin concentrations were measured by HPLC. Apparent elimination half-life and apparent plasma clearance were the same in both groups, 0.8 +/- 0.09 h and 27.6 +/- 5.57 l/h, respectively. Nitrofurantoin was not detectable in the milk just before the 4th administration. The amount excreted in the milk within 6 h after nitrofurantoin administration was 22-57 micrograms (I) and 61-284 micrograms (II) which represents 0.05-0.11% (I) and 0.06-0.28 (II) of the nitrofurantoin dose. The nitrofurantoin concentration ratio of the breast milk to the plasma collected at 3 h was 2.2 +/- 1.2 (I) and 2.3 +/- 1.6 (II). These results show that nitrofurantoin excretion in human milk is low: below 0.12 (I) and 0.29% (II). It suggested that breast-fed newborn infants from mothers treated with nitrofurantoin would be exposed to small amounts of drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Pharmacokinetics of intravenous salbutamol in renal insufficiency and its biological effects.

Salbutamol was administered intravenously to 5 patients with renal function impairment for estimation its pharmacokinetic parameters. The mean terminal half-life was 256 min, similar to previously reported values in healthy adults. The mean clearance (167 ml/min) and the mean volume of distribution (551) were decreased. These parameters were not correlated with the creatinine clearance. A slight but significant decrease was observed in the plasma potassium level up to 125 min after the salbutamol infusion. The heart rate was significantly increased, and the increase in 3 patients was correlated with the salbutamol concentration. The biological effects of the drug were less marked than expected.

Acute Kidney Injury↗

PubMed1989

Maturation of AFMU excretion in infants.

The maturation of the N-acetyltransferase-dependent AFMU production from caffeine was studied during infancy. The group of children (N = 14) consisted of 4 premature newborn infants and ten 1-19 month-old infants who received caffeine citrate solution for the treatment and prevention of apnea. Caffeine, AFMU, 1X and 9 other metabolites were measured in urine using HPLC. The AFMU/1X ratio did not vary significantly in this population with increasing age. In one of the infants serially studied, the AFMU/1X ratio increased dramatically between 6 and 12 months of age. This observation suggests that the maturation of N-acetyltransferase activity is not completed before 1 year of age implying that acetylator status cannot reliably be determined before that age. Patients studied before 1 year of age whose AFMU/1X ratio was below 0.4 may be either true slow acetylators or still immature fast acetylators.

Acetylation↗

PubMed1989

Pharmacokinetic interactions between theophylline and rioprostil.

The study is of double-blind crossover design. The effects of rioprostil, an analogue of prostaglandin E1, at a dose of 300 micrograms b.d., and placebo on the kinetic of slow-release theophylline are investigated. Eight healthy male volunteers participate in the study, each study period lasting for one week. During the first period, the doses of theophylline are altered in response to measured theophylline levels, 200 mg or 400 mg b.d. Regardless of placebo or rioprostil treatment, side effects appear before day 6 and are related specifically to theophylline administration. Blood samples are taken on days 4 and 5 to check steady-state plasma levels of theophylline and on days 6 and 7 to determine the main pharmacokinetic parameters. The same schedule is used for the second period of treatment. The achievement of steady-state concentration is verified. The mean pharmacokinetic parameters do not show a significant difference when slow-release theophylline is given alone or with rioprostil. These results are likely to be clinically relevant and, therefore, the theophylline dose should not be changed if rioprostil is prescribed at the same time as the theophylline.

Adult↗