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Biomedical subjects

E Rey

Publications and source records attributed to E Rey.

At least 163 records · Page 9Linked to original sources
PubMed1980

Pharmacokinetics of buflomedil after intravenous and oral administration.

Pharmacokinetics studies were conducted in 4 patients who received buflomedil 100 mg intravenously and in 3 volunteers who received buflomedil 450 mg per os. Buflomedil concentrations were determined by a gas liquid chromatography method. Buflomedil levels declined multiphasically with a mean clearance after intravenous administration of -0,034 (1 h-1 kg-1). The decline appeared to be monophasic after oral administration. In both cases the overall half-life is short, mean 2.07 hrs (range, 1,47-2,6 hrs).

Administration, Oral↗
PubMed1979

Transfer in vitro of three benzodiazepines across the human placenta.

A comparative study of the placental transfer to the foetus of three benzodiazepines was performed using a dual perfusion system of the human placental lobule. A transport fraction was calculated for each benzodiazepine and was compared with reference substances. Relative to antipyrine, the transport fraction of diazepam was 85%, and that of nordiazepam was 84%. The transport fraction of clorazepate represented only 20% of that of tritiated water. The relatively high transfer of diazepam and nordiazepam can be attributed to their high lipid solubility, and the lower transfer of clorazepate is due to its polar nature. It is suggested that in certain instances this benzodiazepine may be of especial value to obstetricians.

Anti-Anxiety Agents↗
PubMed1979

Pharmacokinetics of clorazepate in pregnant and non-pregnant women.

A single dose of clorazepate 20 mg was injected i.m. in 7 pregnant and 7 non-pregnant women. Blood samples were collected for one week, and urine was collected for 24 h after the dose. The concentrations of clorazepate and its metabolite nordiazepam were determined by electron capture gas liquid chromatography. There was no difference between the two groups on physical examinations. Clorazepate was rapidly absorbed and the peak concentration was reached within 2 h. Mean pharmacokinetic parameters for clorazepate were absorption half life 0.77 h in pregnant women and 0.56 h in non-pregnant women; elimination half life 1.3 h in pregnant women and 2.0 h in non-pregnant women; volume of distribution: 0.43 1 . kg-1 in the pregnant women and 0.33 1 . kg-1 in non-pregnant women. Nordiazepam reached its peak concentration within 12 h after dosing; its mean half life of elimination was 180 h in pregnant women and 60 h in non-pregnant women. Within 24 h, 1.3% of the clorazepate was recovered in urine from pregnant women and 7% in urine from the non-pregnant women.

Adult↗
PubMed1979

Pharmacokinetics of the placental transfer and distribution of clorazepate and its metabolite nordiazepam in the feto-placental unit and in the neonate.

Clorazepate 20 mg was given i.m. to 49 mothers during the first stage of labour. The elimination of the drug was studied in 27 newborns produced by these mothers. The same dose was given to 13 women who underwent amniocentesis and to 7 women who were breast-feeding. "Total nordiazepam", i.e. the sum of clorazepate and its metabolite nordiazepam, was determined by gas-liquid chromatography in maternal blood, umbilical cord blood (both arterial and venous), amniotic fluid and in milk. Clorazepate was found to cross the placental barrier slowly, but nordiazepam was transferred more rapidly. Nordiazepam was found in the milk and in the blood of neonates after breast-feeding had started.

Adult↗
PubMed1979

Pharmacokinetics of carbamazepine in the neonate and in the child.

1. Pharmacokinetic of carbamazepine were made in 7 new-borns and in 5 children. They were hospitalized for epilepsy and were receiving drugs such as phenobarbital alone or in association with other antiepileptic drugs, but not with carbamazepine. 2. The drug was given by oral route with a mean dose of 17.2 mg.kg-1. 3. The determination of carbamazepine concentration in serum was made by gas liquid chromatography on a 50 microliter sample. 4. A one compartment body model was used to determine the pharmacokinetic constants with first order rate constants for absorption and elimination. 5. Absorption was generally delayed by about half an hour, the maximum concentrations ranging from 3.14 to 10 microgram.ml-1 at 2 and 9 hr after administration. The mean half-life for absorption was 1.42 +/- 0.34 hr. The mean half-life for elimination was 8.76 +/- 0.85 hr. The half-life for elimination was much shorter than those already described even in multiple dosing epileptic adult patients. The pharmacokinetic parameters were used to predict blood levels in chronic treatment in 3 children. The predicted steady state concentrations disagreed with the concentrations measured.

Adult↗
PubMed1978

Plasma hypoxanthine in neonatal hypoxia: a comparison of two methods.

Hypoxanthine levels were determined in both venous and arterial cord blood of 42 neonates. Two methods were compared, a PO2 electrode determination and an HPLC (high-pressure liquid chromatography) method. A good correlation was found between the two methods. However, the HPLC method was more sensitive, more reproducible and easier to perform. Hypoxanthine levels in the umbilical artery were found to be higher than in the vein. A significant negative correlation between pH and hypoxanthine level was established. The studies showed that plasma hypoxanthine levels by themselves did not provide an absolute diagnosis of intrauterine hypoxia.

Blood Gas Analysis↗
PubMed1978

[Determination of dipotassium clorazepate in the plasma by gas chromatography (author's transl)].

The authors present a method of estimation of dipotassium clorazepate by gas chromatography with a detector for electron capture. It requires 2 ml of blood. Two separate extractions are necessary, including one immediately after the sampling to determine the nordiazepam present at the time of the blood sample. The second extraction permits one to determine the total nordiazepam obtained by transformation of all the dipotassium clorazepate. This method is simple and rapid and permits one to determine with precision, specificity and good reproducibility (CV -- 3%) the therapeutic concentrations of this drug.

Anti-Anxiety Agents↗
PubMed1977

Micromethod for determination of diazepam by electron-capture gas-liquid chromatography.

We used 100 microliters of plasma for the determination of diazepam. After the internal standard, prazepam, is added, the serum is directly extracted with diethyl ether, the extract is evaporated, the residue is dissolved in ethanol, and the drug is measured by gas-liquid chromatography, with use of an electron capture detector. With this procedure, 2.5 ng of diazepam in the sample can be speedily measured with specificity, accuracy, and reproducibility (CV = 4.5%).

Chromatography, Gas↗
PubMedDate not supplied

Effect of pregnandiol on caffeine metabolism in female rats.

Three groups of six 5-week-old Sprague Dawley female rats received i.p. injections of pregnandiol, 1.25, 2.50 or 5 mg/kg, respectively, in triolein daily for 7 days. Caffeine metabolism was studied in liver slices on day 8 by HPLC. Only primary metabolites were formed. N-1 demethylation was the most important pathway (theobromine represented 51% of total dimethylxanthines). Unlike in human in vitro or in vivo, 1,3,7-DAU (6-amino-5-(N-formylmethylamino)-1,3-dimethyluracil) was an important metabolite (9.7% of total caffeine metabolites). Pregnandiol inhibited N-1, N-3 and N-7 demethylation in vitro (-33%, -33% and -28%, respectively, at 5 mg/kg/day), but it had no effect on N-1 demethylation at 1.25 or 2.50 mg/kg/day. Pregnandiol at all doses had no effect on 1,3,7-trimethyluric acid and 1,3,7-DAU formation. These results are consistent with the hypothesis that C-8 hydroxylation and demethylation of caffeine are mediated by different isoenzymes. They indicate that pregnandiol is a potent inhibitor of microsomal drug metabolism, specifically of cytochrome P450 IA, which could explain the immaturity of some metabolic pathways of caffeine in neonates.

Animals↗
PubMedDate not supplied

Effects of transdermal nitroglycerin in children with congestive heart failure: a Doppler echocardiographic study.

The aim of this study was to evaluate by Doppler echocardiography whether administration of transdermal nitroglycerin (NTG) to children with congestive heart failure could modify mitral flow velocity profile with redistribution of left ventricular filling to late diastole, suggesting preload reduction of the left ventricle. Twelve children with congestive heart failure, aged from 6 months to 6 years (2.83 +/- 2.24 years; mean +/- SD), were recruited. Patients were randomly allocated either a NTG patch (study group; n = 6) or a placebo patch (control group; n = 6) in a double-blind procedure. The NTG patch was a 10-cm(2) patch releasing 5 mg of NTG per day. NTG patches were adjusted to a dose of 1 cm(2)/kg/day (0.5 mg/kg/day). Peak velocity and time--velocity integral (TVI) of E and A waves of transmitral flow, the ratio of the velocities of the A wave and E wave, and the ratio of the TVI of the A wave to the TVI of the E wave were measured. Doppler measurements were determined before treatment (H0) and 4 hours (H4) and 23 hours (H23) after the patch application. Relative changes of these parameters were not significantly different between these two groups. In the NTG group, mean NTG plasma concentration was 1.08 +/- 0.47 microg Liter(-1) at H4 (n = 5) and 1.18 +/- 0.81 microg Liter(-1) at H23 (n = 5). No patient had a NTG plasma concentration greater than 2 microg Liter(-1) either at H3 or at H24. These data suggest that 1 cm(2)/kg transdermal doses of NTG may have a limited bioavailability or a higher clearance and minimal hemodynamic effects in children with congestive heart failure already receiving other medications, implying that higher doses should be used.

Administration, Cutaneous↗
PubMedDate not supplied

[Effects of therapy (diazepam, phenobarbital) on the E.E.G. in new-born babies during the first 24 hours of treatment (author's transl)].

The poor prognostic significance of inactive or paroxystic E.E.G. recordings in new-born babies appears to be well established (Monod et al., ibid., 1972, 32, 529-544). However, some cases have been described as having a favourable evolution even though such tracings had been proesent during the neonatal period. The authors studied, therefore, the effects of anticonvulsants (diazepam, phenobarbital) to see if they produced inactive or paroxystic tracings. A total of 19 new-born babies with convulsions of various etiologies were treated with phenobarbital and diazepam and recordings were made less than 24 hours after the beginning of treatment. Plasma levels were measured at the time of recording and varied from 3 to 26 micrograms/ml for phenobarbital and 0 to 2.75 micrograms/ml for diazepam. No paroxystic tracings were noted, but 2 inactive tracings were seen in infants who had been severely asphyxiated at birth, and in whom the plasma levels of the anticonvulants was found to be low. The injection of diazepam during the E.E.G. recording caused suppression of electrical discharges without notably altering the inter-seizure E.E.G. activity. The authors conclude that in the 19 cases studied the changes noted in the E.E.G. were related to the severity of the condition and were not secondary to therapy.

Diazepam↗
PubMedDate not supplied

Influence of aspirin on the hemodynamic effects of sublingual nitroglycerin.

We studied the possible interaction between aspirin and nitroglycerin (NTG) in seven healthy volunteers. Effects of NTG (0.8 mg sublingual spray) were assessed by the decrease in diastolic arterial pressure, increase in heart rate, and decrease in M-mode echocardiographic end-diastolic and end-systolic diameters of the left ventricle. Measurements were performed before and during 30 min after NTG. Plasma levels of NTG were monitored during the experimental procedure. Each of the following trials was repeated three times, in random order, in each volunteer: NTG without aspirin pretreatment, NTG 1 h after 1 g of oral aspirin, and NTG after 8 days of aspirin, 500 mg every 48 h. Aspirin at the 1-g dose level significantly increased the effects of NTG on diastolic blood pressure (p less than 0.05) and left ventricular end-diastolic (p less than 0.001) and end-systolic (p less than 0.001) diameters. Aspirin (1 g) significantly increased (p less than 0.01) mean NTG plasma levels from 0.24 +/- 0.13 ng . ml-1 (control) to 0.37 +/- 0.26 ng . ml-1. We conclude that pretreatment with 1 g of aspirin increases NTG plasma levels and therefore significantly enhances the pharmacodynamic effects of NTG.

Adult↗