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G Lachatre

Publications and source records attributed to G Lachatre.

At least 19 recordsLinked to original sources
PubMed2000

High-performance liquid chromatographic determination of tianeptine in plasma applied to pharmacokinetic studies.

An improved analytical method for the quantitative measurement of tianeptine and its main metabolite MC5 in human plasma was designed. Extraction involved ion-paired liquid-liquid extraction of the compounds from 1.0 ml of human plasma adjusted to pH 7.0. HPLC separation was performed using a Nucleosil C18, 5 microm column (150x4.6 mm I.D.) and a mixture of acetonitrile and pH 3, 2.7 g l(-1) solution of sodium heptanesulfonate in distilled water (40:60, v/v) as mobile phase. UV detection was performed using a diode array detector in the 200-400 nm passband, and quantification of the analytes was made at 220 nm. For both tianeptine and MC5 metabolite, the limit of quantitation was 5 microg l(-1) and the calibration curves were linear from 5 to 500 microg l(-1). Intra- and inter-assay precision and accuracy fulfilled the international requirements. The recovery of tianeptine and its metabolite from plasma was, respectively, 71.5 and 74.3% at 20 microg l(-1), 71.2 and 70.8% at 400 microg l(-1). The selectivity of the method was checked by verifying the absence of chromatographic interference from pure solutions of the most commonly associated therapeutic drugs. This method, validated according to the criteria established by the Journal of Chromatography B, was applied to the determination of tianeptine and MC5-metabolite in human plasma in pharmacokinetic studies.

Antidepressive Agents, Tricyclic↗
PubMed2000

Fatal intoxication following self-administration of a massive dose of buprenorphine.

Several drug packages, including Subutex (high-dose buprenorphine, as sublingual tablets) boxes, were found near the corpse of a 25-year-old male drug addict, who apparently had committed suicide. The autopsy revealed a fatal respiratory depression. The toxicological investigations concluded that death resulted from massive burpienorphine intoxication. The determination of buprenorphine (BU) and norbuprenorphine (NBU) in all biological specimens was performed by liquid chromatography-electrospray mass spectrometry (LC-ES-MS) after hydrolysis (for solid tissues), deproteinization of the matrices, and solid-phase extraction of the compounds. Exceptionally high concentrations of BU and NBU were found in blood (3.3 and 0.4 mg/L, respectively), urine (3.4 and 0.6 mg/L), bile (2035 and 536 mg/L and brain (6.4 a nd 3.9 microg/g). The high concentration of BU (899 mg/L) and the absence of NBU in gastric liquid suggested oral intake. High concentrations of amino-7-flunitra/epam, the main metabolite of flunitra/epam, were also found in blood, urine and gastric liquid. This benzodiazepine may have been a co-factor in the toxic effects of BU.

Adult↗
PubMed1998

Decrease of serum paraoxonase activity in chronic renal failure.

Paraoxonase is an esterase that hydrolyzes organophosphate compounds. The enzyme is associated with HDL and could protect LDL against peroxidation, which suggests a possible involvement of paraoxonase in the antiatherogenic properties of HDL. Paraoxonase activity has been shown to be low in patients with myocardial infarction, diabetes mellitus, or familial hypercholesterolemia. Because cardiovascular disease is the main cause of death in chronic renal failure, serum paraoxonase activity was measured by spectrophotometry using three synthetic substrates (phenyl acetate, paraoxon, and 4-nitrophenyl acetate) in 305 patients with kidney disease, including 47 patients with non-end-stage chronic renal failure, 104 patients treated with hemodialysis, 22 patients treated with peritoneal dialysis, and 132 renal transplant patients. Patients were compared with two groups of aged-matched control subjects (total number = 195). Especially with 4-nitrophenyl acetate, paraoxonase activity was lower in patients with some degree of renal insufficiency (chronic renal failure [P < 0.05], chronic hemodialysis [P < 10(-4)], chronic peritoneal dialysis [P < 10(-4)]) than in control subjects. In transplant patients, paraoxonase activity was not found to be different from that in control subjects. The decrease of paraoxonase activity and thus the reduction of its antiatherogenic properties in renal failure could be an essential factor of premature vascular aging, especially when dialysis is used. Renal transplantation seems to restore paraoxonase activity.

Adolescent↗
PubMed1998

[Lead intoxication and amyotrophic lateral sclerosis].

A seventy-six-year-old patient developed a bulbar form of amyotrophic lateral sclerosis, after chronic lead intoxication from drinking water. Treatment with 2,3 dimercaptosuccinic acid was administered for six months and had no effect on clinical course. We discuss the imputability of lead as a possible etiological factor.

Aged↗
PubMed1997

Separation of cardiac glycosides by micellar electrokinetic chromatography and microemulsion electrokinetic chromatography.

The interest of micellar electrokinetic chromatography (MEKC) and microemulsion electrokinetic chromatography (MEEKC) for the resolution of four cardiac glycosides is demonstrated. First, the influence of some parameters on the resolution of the solutes in MEKC such as the concentration of the surfactant, pH, addition of organic modifiers and urea is discussed. Then, results are compared with those obtained in MEEKC using different microemulsion compositions. Results indicate that MEEKC possesses several advantages over MEKC for the separation of relatively hydrophobic compounds such as digitalic compounds. First, microemulsions allow a better manipulation of the migration time window and of the retention of the solutes. Moreover, efficiency is improved with shorter analysis time.

Acetyldigitoxins↗
PubMed1997

Serotonin syndrome due to an overdose of moclobemide and clomipramine. A potentially life-threatening association.

The serotonin syndrome is frequently characterized by minor neurologic manifestations that regress rapidly (such as confusion, tremor, ...). Many medications including tricyclic antidepressants, serotonin reuptake inhibitors, tryptophan and the association of monoamine oxidase inhibitors together with a serotoninergic agent have been implicated in this syndrome. In certain cases, and for poorly understood reasons, clinical manifestations can include circulatory collapse, malignant hyperthermia, convulsions and rhabdomyolysis. These forms are often fatal. Treatment, other than the withdrawal of the offending drug, is symptomatic. Dialysis may be of value in withdrawing the drug from the circulatory system. We report a patient with the serotonin syndrome of favorable outcome due to an overdose of moclobemide and clomipramine.

Antidepressive Agents↗
PubMed1996

The role of hyaluronidase on lidocaine and bupivacaine pharmacokinetics after peribulbar blockade.

Orbital regional anesthesia is the only circumstance where hyaluronidase is routinely added to local anesthetics to accelerate the onset of the block. The aim of this study was to compare the pharmacokinetics of lidocaine and bupivacaine with or without hyaluronidase for peribulbar blockade. Twenty-one patients scheduled for cataract surgery with lens implantation were included in this prospective randomized study. Peribulbar blocks were achieved with plain bupivacaine 0.5% (5.5 mL), lidocaine 2% (5.5 mL), and hyaluronidase (100 IU = 2 mL) (n = 10) ir sterile water (2 mL) (n = 11). Plasma bupivacaine and lidocaine concentrations were measured by high-performance liquid chromatography at regular intervals from the end of the local anesthetic injection until the 360th minute. Maximum plasma concentration (Cmax) and time to reach Cmax (Tmax) were obtained for all the patients except one who needed a supplementary injection and was excluded from the study. The time to onset and duration of the analgesia and akinesia were monitored at the times of sampling. Motor blockade was incomplete in two patients in each group without affecting surgery. The Tmax and absorption half-life (t1/2a) of lidocaine and bupivacaine were not different within each group (P > 0.05). The Tmax of lidocaine was shorter in the presence of hyaluronidase (17.1 +/- 2.6 min vs 32.7 +/- 6.0 min) as well as the Tmax of bupivacaine (16.8 +/- 3.0 min vs 26.5 +/- 4.4 min). The Cmax of lidocaine and bupivacaine were not modified by the addition of hyaluronidase. The clearance, terminal half-life, and volume of distribution were not different between groups. The absorption of lidocaine and bupivacaine from the peribulbar space are hastened by the addition of hyaluronidase. The Tmax of lidocaine is not different from that of bupivacaine within each group suggesting that the absorption of local anesthetics is minimally influenced by the liposolubility of the drugs. Moreover, hyaluronidase influences the absorption kinetics of both lidocaine and bupivacaine in the same manner.

Absorption↗
PubMed1995

[Pharmacokinetics of lidocaine and bupivacaine after peribulbar block with additional hyaluronidase].

OBJECTIVE: To assess the time course of plasma concentrations of lidocaine and bupivacaine associated with hyaluronidase for peribulbar block. STUDY DESIGN: Prospective study. PATIENTS: Ten patients (mean age = 71 +/- 11 yrs, mean weight 63 +/- 10 kg) scheduled for cataract surgery with lens implantation. METHOD: Lidocaine 2% (5.5 mL = 110 mg) and bupivacaine 0.5% (5.5 mL = 27.5 mg) associated with hyaluronidase (80 IU) were injected supra and infra-orbitally, in patients premedicated with midazolam. Blood samples wer0 collected at constant time intervals from the end of infiltration until the 6th hour. The plasma concentrations of local anesthetics were measured with the HPLC technique. RESULTS: The median plasma peak concentration was 1.74 mg.L-1 after 10 min for lidocaine, and 0.52 mg.L-1 after 7.5 min for bupivacaine respectively. CONCLUSIONS: The similar delays of occurrence of peak concentrations confirm that liposolubility is not the only factor of diffusion of local anaesthetics from the periocular fat into the blood stream. The peak concentrations are far below the alleged toxic concentrations. When associated with hyaluronidase, the peak concentrations occur as rapidly as after endotracheal or paracervical administration.

Aged↗
PubMed1995

Comparison of 2- and 3-compartment models for the Bayesian estimation of methotrexate pharmacokinetics.

Moderate and high-dose methotrexate was given by a 4-h infusion to 10 patients. The pharmacokinetics of methotrexate, determined by fluorescence polarization immuno-assay, was successively described by a 2- and a 3-compartment open model with elimination from the central compartment. Population pharmacokinetic parameters were obtained by non-linear regression from 8 data points for each course and were subsequently used to fit the same data by the Bayesian estimation method. According to Akaike's information criterion, the 3-compartment model was found statistically superior in 7 patients out of 10. Using this model clearance was well predicted (+/- 5%) by the Bayesian method with only 2 points taken at the end of the infusion and 24 h after. The prediction was less good for the steady-state volume of distribution (+/- 18%) and the half-lives (+/- 20-30%). This procedure enables a good estimation of individual pharmacokinetic parameters for methotrexate, specially with clearance, at minimal cost and minimal disturbance for the patient.

Adolescent↗
PubMed1994

Pharmacokinetics and dosage regimens of amikacin in intensive care unit patients.

The pharmacokinetics of amikacin have been studied in 40 intensive care unit (ICU) patients using a two-compartment model and the Bayesian estimation method implemented in the USC PC-PACK program of Jelliffe et al. The volume of the central compartment was significantly higher in these patients (0.36 l.kg-1) than in the reference population (0.20 l.kg-1). A method has been designed to compute dosage regimens in order to maintain a constant steady-state average plasma concentration of 8 mg.l-1 for repeated i.v. infusions. The regimen calculated for the 'average' ICU patient varies between 11 mg.kg-1 three times per day for the patient with normal renal function and 6 mg.kg-1 every 2 days for the anuric patient. This regimen is intended to begin amikacin therapy in an ICU patient, while the population pharmacokinetic parameters would allow the individualization of the regimen by means of the Bayesian method.

Amikacin↗
PubMed1993

[Pharmacokinetics of epidural or intrathecal bupivacaine in elective cesarean section].

Twenty ASA 1 pregnant women at term, undergoing elective Caesarean section were included in this study. They were randomly assigned to one of two groups, receiving either a spinal or an epidural anaesthesia. Before induction, in order to prevent hypotension, all patients were given an i.v. infusion of 1000 ml of Ringer-lactate and a subcutaneous injection of ephedrine 30 mg. They were positioned on the operating table with a 15 degrees left lateral tilt. Spinal anaesthesia was performed with hyperbaric bupivacaine 0.5 p. cent (0.08 mg.cm-1 of height). Epidural anaesthesia was obtained with a bolus dose of 0.5 p. cent plain bupivacaine, followed by a continuous infusion through the epidural catheter until the level of surgical block reached T6 bilaterally. Bupivacaine was assayed in plasma by high performance liquid chromatography (HPLC). Following pharmacokinetic parameters of bupivacaine were determined: Cmax (maximal concentration), Tmax (time to reach maximum), AUC (area under curve), Cl (total plasma clearance), Vz (volume of distribution during the elimination phase), T1/2 (elimination half-life). Bupivacaine concentration was also measured in samples obtained at birth from umbilical vein and umbilical artery. The mean dose of bupivacaine used was 12.8 +/- 0.6 mg in the spinal group and 118.6 +/- 17.8 mg in the epidural group. The time of onset of surgical anaesthesia was significantly shorter with spinal anaesthesia (7.6 +/- 4.4 vs 31 +/- 11.1 min; p < 0.01). The sensory block had a longer duration in epidural group (223.2 +/- 15 vs 291 +/- 13.8; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural↗
PubMed1993

Pharmacokinetics of propofol and its conjugates after continuous infusion in normal and in renal failure patients: a preliminary study.

The pharmacokinetics of propofol, 2,6 diisopropylphenol, were compared in 6 end-stage renal failure patients aged 66.3 +/- 12.1 years and in 5 normal patients aged 45.5 +/- 13.5 years. Anesthesia was induced with propofol (2 and 2.5 mg.kg-1 respectively) and fentanyl (0.1 mg). Anesthesia was maintained with propofol (9 and 10 mg.kg-1 x h-1 respectively). Patients breathed spontaneously a 50 per cent oxygen in nitrous oxide mixture. Two ml blood samples were taken during anesthesia and at regular intervals until up to 24 hours after infusion. Plasma levels of propofol were determined by HPLC with electrochemical detection. Propofol conjugates were determined after hydrolysis with beta glucuronidase or HCl. Results were expressed as median [lower-upper percentiles]. Propofol clearance (1.53 [1.02-2.10] L.min-1 x kg-1 versus 1.65 [1.39-1.78] L.min-1 x kg-1 in normal patients), and half-lives elimination were not modified by renal failure. Renal failure patients exhibited a higher volume of distribution at steady state as compared to normal patients (19.28 [11.71-76.81] L.kg-1 versus 8.60 [6.58-9.81] L.kg-1, p < 0.05). Renal failure did not affect the production of conjugates but they accumulated in blood of renal failure patients. Despite this, no difference in time to eyes opening and propofol concentration were observed, confirming the absence of clinical effect of these metabolites.

Adult↗
PubMed1992

Pharmacokinetics of vinorelbine in man.

The pharmacokinetics of vinorelbine has been investigated by a new HPLC method in 8 cancer patients receiving 8 weekly doses (30 mg.m-2) administered by brief infusion (15 min). The plasma concentration-time curves showed a tri-exponential decay with a long terminal half-life (44.7 h) and a high volume of distribution (Vz = 75.61.kg-1). The concentrations after the 8th infusion were significantly lower than after the 1st infusion, but without significant modification of CL (1.28 l.h-1.kg-1) or AUC (0.80 mg.l-1.h). The pharmacokinetic parameters exhibited wide interindividual variations. The results are consistent with those of previous RIA studies, although the HPLC method appears to be more specific and more precise.

Aged↗
PubMed1992

Population pharmacokinetic parameters for Bayesian monitoring of amikacin therapy in intensive care unit patients.

The pharmacokinetics of amikacin has been studied in 40 intensive care unit patients using the bayesian estimation method implemented in the USC PC PACK program of Jelliffe. The volume of the central compartment was significantly higher in these patients than in the reference population, while other pharmacokinetic parameters did not differ significantly from the reference values. The population values may be employed, in addition to those supplied with the software, to adapt dosage regimens of amikacin in ICU patients.

Adolescent↗
PubMed1991

Antibiotic levels in bronchial tree and in serum during selective digestive decontamination.

Selective digestive decontamination has been found to prevent pulmonary infections in mechanically ventilated patients. The aims of this study were: 1) to determine whether detectable levels of antibiotics could be found in bronchial tree secretions of patients receiving SDD, and 2) to evaluate antibiotic serum levels. In 15 patients receiving mechanical ventilation and SDD for 10 days or more, tobramycin and amphotericin B levels were determined every 3 days in the following specimens: tracheal aspirates, distal bronchial secretions and blood samples. 82% of tracheal aspirates contained detectable (greater than 0.18 mg/l), tobramycin concentrations; the levels varied widely between patients and large day-to-day variations were observed. Every patient had at least 1 tracheal aspirate with tobramycin level higher than 0.5 mg/l during his course. 40% of distal specimens contained detectable tobramycin levels (10 patients). Serum determinations showed detectable concentration of tobramycin in 50% of the specimens (9 patients). Two patients with renal failure had serum tobramycin levels higher than 2 mg/l. In 13 tracheal aspirates cultures were positive and 15 species were isolated; 13 had a MIC higher than the corresponding tobramycin level in tracheal secretions. We conclude that substantial levels of antibiotics can be found frequently in respiratory tract specimens of patients receiving SDD. Therefore, the usual microbiological criteria used to assess respiratory tract infection may be unreliable in this setting and other criteria may be required. Follow-up of antibiotic serum levels is required, especially in patients with renal failure.

Acute Kidney Injury↗
PubMed1989

Pharmacokinetics of amineptine after single-dose, repeated treatment and study of the at-risk populations.

In this paper, three different studies are discussed. First, pharmacokinetics of the tricyclic antidepressant amineptine (Survector) and its main metabolite were investigated in young healthy adults. Amineptine was rapidly absorbed. Mean peak plasma concentrations of amineptine and its metabolite occurred 1 and 1.5 h, respectively, after drug administration. The mean apparent volume of distribution was large: 2.4 L/kg. Elimination was rapid. T 1/2 (half-life) was 0.8 h for amineptine and 2.5 h for the metabolite. The mean apparent plasma clearance of amineptine was high (124.8 L/h). In a second study in young patients, no change in pharmacokinetic parameters was observed after a 10-day course of repeated treatment with the drug. Finally, pharmacokinetics of amineptine and its main metabolite were studied in elderly patients on day 1 and after a repeated administration for 15 days. There was no significant age-linked change in the pharmacokinetics of amineptine even if half-life and area under the curve of the metabolite were all greater in the elderly subjects than in young adults. Pharmacokinetic parameters of amineptine and its metabolite were not affected by repeated administration over 15 days. The pharmacokinetic characteristics of amineptine in elderly subjects do not necessitate any dosage alteration for this population.

Adult↗