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Biomedical subjects

A Brachet-Liermain

Publications and source records attributed to A Brachet-Liermain.

At least 19 recordsLinked to original sources

Failure of falciparum malaria prophylaxis by mefloquine in travelers from West Africa.

Due to the spread of chloroquine-resistant strains of Plasmodium falciparum in French speaking parts of Africa, we have found it necessary to prescribe mefloquine for antimalaria prophylaxis to travelers to this area. Weekly doses of 125 or 250 mg have been recommended for short journeys. In spite of this regimen, 16 documented cases of falciparum malaria in travelers have been recorded in the Bordeaux hospital center since October, 1988. Fifteen of these patients were tourists returning from West African countries, and one was an Ivorian student who had been on vacation to his home country. Nine of these patients were evaluated and found to have high plasma mefloquine levels. This report strongly supports the existence of mefloquine-resistant falciparum malaria in West Africa, especially in Sierra Leone, Burkina Faso, and Cote d'Ivoire.

Adult↗

[Transplacental passage of doxorubicin].

The transplacental passage of doxorubicin, an anthracycline used for lymphoproliferative disorders and breast cancer, was studied by in vitro perfusion of term human placenta. Placentas from women with uncomplicated pregnancy were collected immediately after vaginal delivery and put into a 37 degree C thermostatically-controlled hood. A cotyledon was chosen and placed into the perfusion chamber; fetal and maternal compartments of the isolated lobe were thus perfused with separated "open" circuits. Perfusion of fetal surface of the placenta was started immediately at a flow rate of 6 ml/mn and then so was the perfusion of the intervillous space at a rate of 12 ml/mn. Perfusion medium used was Earle's solution. Antipyrine, to validate experience, and doxorubicin were added to the maternal perfusate. Samples were collected from arterial inflow and venous outflow respective of the maternal and fetal compartment and timed measurements of the fetal venous return were used to calculate flow rates. After a stability study of doxorubicin solutions under experimental conditions, the transplacental transfer of doxorubicin was then investigated for three doses: 3 mg/l, 30 mg/l and 150 mg/l. The global transfer value is low (2.96% +/- 0.75%) and doesn't seem dose-dependent. Adriamycinol, a plasma doxorubicin metabolite, has not been found even for the greatest concentration. The low transfer value can explain the rarity of fetal accidents in clinical reports.

Doxorubicin↗

[Pharmacokinetics of pethidine after spinal anesthesia. Clinical implications].

Eleven male patients undergoing endoscopic resection for prostatic adenoma and bladder tumours under spinal anaesthesia received intrathecal pethidine 1 mg X kg-1. Plasma concentration and its evolution with time were assessed; pethidine plasma concentrations were determined by high performance liquid chromatography. Pethidine was rapidly and extensively absorbed. The peak plasma concentration of pethidine was 176 +/- 66 ng X ml-1 (range: 84-208) and the time to peak concentration was 2.3 +/- 1.4 h (range: 0.5-6 h). The terminal elimination half-life was 7.2 +/- 2.2 h (range: 4-11.5 h). The plasma concentrations of pethidine remained below 500-700 ng X ml-1, the minimum concentration necessary to obtain a systemic analgesic effect. Two patients required noramidopyrine as a complement at the 8th and 12th h respectively. No respiratory depression was observed. Intrathecal pethidine (1 mg X kg-1) was an effective agent for spinal anaesthesia: the prolonged postoperative analgesia was due to the drug acting on opioid receptors in the spinal cord. This led to the necessity of postoperative monitoring during 24 h after intrathecal pethidine administration.

Aged↗

High-dose thiopental pharmacokinetics in brain-injured children and neonates.

High-dose thiopental was administered in 8 children with uncontrollable seizures or hypoxic encephalopathy (group A) and 7 full-term neonates with neonatal asphyxia (group B). All of them were submitted to artificial hyperventilation to maintain pCO2 near 3.5 kPa. Rectal temperature was kept at about 35 degrees C. Thiopental was infused with a rate of 2-4 mg X h-1 X kg-1, with treatment lasting 32-192 h for group A (mean 103 h), and 36-48 h for group B (mean 38.5 h). Plasma concentration-time data were analysed pharmacokinetically. Thiopental elimination half-life was 14.5 h (group A) and 20.9 h (group B). The clearance of thiopental was 0.27 liters X h-1 X kg-1 (group A) and 0.32 liters X h-1 X kg-1 (group B). The volume of distribution at steady-state was 5.41 liters X kg-1 (group A) and 8.26 liters X kg-1 (group B). These results show that high-dose thiopental pharmacokinetics is not very different for full-term newborns, children and adults. Elimination half-life and volume of distribution are changed when compared to single-dose studies, while clearance is only slightly modified. The time for disappearance of thiopental from blood is also very long (2 to 5 days). These pharmacokinetic characteristics would be worthy of consideration in cases where there may be prolonged use of thiopental, considering the risk of accumulation and toxicity.

Brain Diseases↗

[Ceftriaxone and severe infections in medical resuscitation].

Ceftriaxone was used in 24 medical intensive care patients to treat 8 pulmonary infections, 12 septicaemias, 3 urinary tract infections, 1 meningitis. It was administered at a single intravenous dose of 2 g every 24 h. The therapy was successful, clinically and bacteriologically in 16 patients. The reasons of the failures are analysed. Plasma concentrations were obtained: they demonstrate that ceftriaxone is effective when given once a day in most cases.

Adult↗

[Determination of blood ceftriaxone. Comparison of microbiological and HPLC methods].

108 serum samples in 27 patients were collected after the first, before the second, after and before the fifth dose of 2 g every 24 h and assayed for ceftriaxone by microbiological method and high pressure liquid chromatography (HPLC). The statistical analysis of the results show a correlation coefficient equal to 0.95. The protein binding doesn't affect the microbiological method. The two methods are convenient for clinical use.

Bacteriological Techniques↗

[Clinical evaluation of ceftriaxone in severe infections in adults].

Thirty patients (17 male, 13 female; age 17 to 84 years; normal renal function in 23 cases) with severe bacterial infections were treated with ceftriaxone. The infections was septicemia in 20 cases, a septicemia-like condition in 2 and a focal infection in 8 (2 abscesses of the lung, 2 pyelonephritis, 1 abscess of the liver, 1 subphrenic abscess, 1 meningitis developed from an abscess of the brain and 1 acute intestinal infection). 25 infections were bacteriologically documented, with recovery of the following pathogens: 20 Gram negative rods (including 10 E. coli) that were all susceptible to ceftriaxone (MIC = 0.02 to 0.5 mg/l) except 2 (1 Pseudomonas and 1 E. cloacae), 5 susceptible Gram positive cocci (3 Pneumococcus, 1 Streptococcus and 1 Staphylococcus epidermidis) and 3 susceptible anaerobes (2 B. fragilis and 1 B. melaninogenicus). Ceftriaxone was given alone in 15 cases and in association with another antibiotic in 15 cases (aminoglycoside in 10 cases, nitroimidazole in 4 and fosfomycin in 1). The dose of ceftriaxone was 1 to 2 g per day in 28 cases, 3 g per day in 1 case (meningitis with abscess of the brain) and 1 g every other day in 1 case (chronic renal failure under hemodialysis). Duration of treatment ranged from 10 to 62 days (average 17 days). The usual routes of administration were IV and IM; the SC route was used on 4 occasions. Pharmacokinetic studies of serum levels were carried out in several patients including two who had ceftriaxone subcutaneously; results were consistent with those previously reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[A rapid method for the determination of cyclosporin A in blood by high performance liquid chromatography].

The purpose of this paper is to propose a method for the determination of cyclosporin in whole blood by means of HPLC with UV detection. After a one step extraction into ether, the organic layer is washed NaOH and evaporated to dryness. The residue is reconstituted in a mixture of acetonitrile and water (40/60) (V/V) and injected into the chromatograph. The C8 reversed phase column is warming at 75 degrees C temperature. The mobile phase consists of acetonitrile and water (60/40) (V/V) and the wavelength is set at 210 nm. The technique is rapid, sensitive, reproducible and well suited for therapeutic monitoring and for pharmacokinetic studies.

Chromatography, High Pressure Liquid↗

[Plasma assay of haloperidol by high performance liquid chromatography].

Haloperidol is extracted with hexane-isoamyl alcohol in the presence of two internal standards, chlorohaloperidol and spiroperidol. For chromatographic separation, a C18 reversed-phase column and a mobile phase of acetonitrile/methanol/phosphate buffer are used. Detection is by UV absorption spectrophotometry at 245 nm, and the limit of detection was set to 1 ng/ml. To study hydroxyhaloperidol, a metabolite of haloperidol which has much less UV-absorption than haloperidol, detection must be seat 220 nm.

Chromatography, High Pressure Liquid↗

Carbamazepine/valproic acid interaction in man and rhesus monkey.

Sodium valproate (VPA) was administered for 1 week (1 g b.i.d.) to seven epileptic patients receiving chronic carbamazepine (CBZ) therapy. Steady-state CBZ levels determined before and after VPA therapy were reduced by 3-59% in six patients and were unchanged in one patient. The plasma concentration ratio of carbamazepine-10,11-epoxide ( CBZE ) to CBZ increased in all patients by 11-500%. The plasma binding of CBZ was determined in six healthy volunteers given a single 400 mg CBZ dose with and without the coadministration of 1 g VPA in a cross-over design. The mean CBZ free-fraction was increased in three of the subjects (p = 0.008-0.031), decreased in one subject (p less than 0.002), and remained unchanged in two subjects when VPA was administered. Four male rhesus monkeys were infused intravenously with CBZ (15 mg h-1) for 5 days and then three consecutive 24-h infusions were given: I, CBZ alone; II, CBZ with 75 mg h-1 VPA; III, CBZ with 150 mg h-1 VPA. The mean free-fraction of CBZ and CBZE increased during infusions II and III from 31.5 +/- 2.7% to 33.6 +/- 2.6% (p less than 0.05) and 37.7 +/- 1.3% (p less than 0.01) for CBZ and from 46.9 +/- 9.2% to 53.6 +/- 5.7% (p greater than 0.05) and 60.1 +/- 4.0% (p less than 0.01) for CBZE . The clearance of free CBZ declined from 7.96 +/- 1.75 to 4.84 +/- 1.26 (p less than 0.01) and 4.12 +/- 1.75 (p less than 0.01) 1 kg-1h-1 during infusions II and III, respectively. The mean free CBZE /CBZ ratio increased from 0.12 +/- 0.03 to 0.24 +/- 0.03 and 0.36 +/- 0.04 during infusions II and III, respectively (p less than 0.001). These findings indicate a decrease in the elimination clearance of CBZE possibly coupled with a decrease in its formation clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Determination of theophylline, phenobarbital and valproic acid by chromatographic and immunologic technics. Comparison of methods].

Theophylline, phenobarbitol, and valproic acid serum levels were measured from plasma samples using chromatographic (HPLC and GC) and by immunologic techniques using enzyme kinetics (EMIT) or fluorescence polarization (FPIA). Results of these various methods differ when examined by more stringent statistical analysis. These differences do not appear to be clinically important except possibly for valproic acid the case in employing immunologic methods as well as their rapidity render these techniques particularly useful for therapeutic surveillance.

Chromatography↗

[Pharmacokinetics of apalcillin. Study of linearity].

Apalcillin is a new semi-synthetic penicillin active on the positive Gram bacteria, and on the enterobacteria, with a particular activity on Pseudomonas and Acinetobacter. The linearity study of the pharmacokinetic was carried out on 26 subjects who were given increasing doses (500, 1 000, 2 000, 3 000 mg) of apalcillin by the venous route. The dosages carried out by the HPLC and bacteriological methods, show a good correlation between the two methods. The serum concentrations, 5 mn. after injection, were respectively 72 micrograms/ml (500 mg); 145 micrograms/ml (1 g) ; 221 micrograms/ml (2 g) ; 290 micrograms/ml (3 g). Urinary excretion is around 20 %, and this, regardless of the dose. The dose increase seems to have no effect on the pharmacokinetic parameters, calculated on the basis of a bi- compartmental model. The areas under the time serum concentrations, increase proportionally, to the dose : 61 (500 mg) ; 146 (1 g) ; 285 (2 g) ; 367 (3 g) - micrograms/ml X h. the linear regression between the AUC (y) and the applied doses (X) is : y = 0,12 X + 14,27 ; r = 0,9046 ; n = 69. The correlation between the AUC and the doses is significant (p less than 0,001). The results obtained show that increasing the dosage has no effect on apalcillin pharmacokinetics, which appear linear.

Adult↗

No effect of food intake on clobazam absorption.

The kinetics of clobazam taken 3 h before, during, and 3 h after a standard hospital meal were studied in six healthy volunteers. Peak plasma levels were significantly lower when the drug was taken with or after meals suggesting that the rate of absorption was reduced by food. The mean area under the concentration vs time curve was not affected by the time of drug administration indicating that the meal had no effect upon the extent of absorption.

Adult↗

[Pharmacokinetic study of apalcillin after infusion].

Apalcillin is a new semi-synthetic penicillin of the uridino-penicillin group. The study comprises two groups of 6 subjects receiving 1 g and 2 g respectively of apalcilline by a two-hour infusion. The assays done by HPLC and microbiology show a good correlation between the two methods. The serum concentrations at the end of the infusion are: 32,2 micrograms/ml-1 (1 g) and 62,7 micrograms/ml-1 (2 g). The modelisation of the serum curves has been realized according to an open model with two compartments. A phase of rapid distribution is observed: t 1/2 alpha of 19.5 mn (1 g), 8.96 mn (2 g) followed by a phase of longer elimination: t 1/2 beta of 1.17 h (1 g), 1.15 h (2 g). The distribution volume at the steady-state is: 14.19 l (1 g), 14.76 l (2 g). This volume, much greater than the plasmatic volume, allows to suppose a good tissular diffusion of apalcilline. The urinary concentrations of the twelve first hours are: 182.64 micrograms/ml (1 g), 323 micrograms/ml (2 g). The urinary elimination during the 24 hours following the administration is: 18.58% (1 g), 16.47% (2 g).

Adult↗

[Preliminary in vitro study of the transplacental passage of spiramycin].

Spiramycin, a true macrolide antibiotic, is the only agent which can be used for the preventive treatment of congenital toxoplasmosis. It gives very high levels in the human placenta, but its transplacental transfer is likely to be very poor, so that it may not cure an already infected foetus. We studied the human placental transfer of spiramycin by an in vitro perfusion model of placentas obtained at term of uncomplicated pregnancies. The transfer rate of spiramycin was found to be close to 9% of the maternal circulating concentrations and 23% of the antipyrine transfer rate, which is only flow-limited. Possible therapeutic implications of these results are discussed.

Antipyrine↗