Biomedical subjects

J Debord

Publications and source records attributed to J Debord.

31 records · Page 2Linked to original sources

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↗

PubMed1990

Acetylcholinesterase inhibition by two phosphoric 4-nitroanilides.

Two phosphoric 4-nitroanilides Z2P(O)NH-phi-NO2 (A, Z = Me; B, Z = NMe2) have been prepared and purified by chromatographic techniques. Their spectral data (uv, ir and 1H-nmr) have been determined, and compared with those of other similar compounds. Their ability to inhibit acetylcholinesterase has been measured by a modification of Ellman's method. The data, as computed according to the Michaelis scheme, indicate that A is not an inhibitor, whereas B is a reversible mixed one. These differences are discussed in terms of hydrophobic interactions.

Acetylcholinesterase↗

PubMed1990

[Sensitivity of the prosobranch mollusk Potamopyrgus jenkinsi Smith to the action of metallic chlorides (ZnCl2, BaCl2, CuCl2) and to the synthetic molluscacide N-tritylmorpholine].

The toxicity of 3 metal chlorides (ZnCl2, BaCl2, CuCl2), and of N-trityl-morpholine (Triphenmorph or frescon) has been studied on the gastropod mollusc Potamopyrgus jenkinsi, in eucalcic and oligocalcic waters. The results showed the following order in the efficiency of the toxic compounds: triphenmorph greater than copper greater than barium greater than zinc. In eucalcic water, the toxicity of barium and decreased whereas the efficiency of triphenmorph and increased. The toxicity of the substances, at middle term, rose in relation to the time of the experiment. An exposure of 2 h to the toxic agents was sufficient to induce high mortality in P jenkinsi. In oligocalcic water, the juvenile snails were more sensitive than the adults to the action of metal chlorides, but they showed higher tolerance to Triphenmorph; in addition, the winter generation was more resistant than the summer one, except for barium.

Animals↗

PubMed1986

[Comparative study of the toxicity of metal chlorides and a synthetic organic molluscacide, N-tritylmorpholine, in 2 fresh-water amphipods, Gammarus pulex and Echinogammarus berilloni].

The effects of three metal salts (BaCl2, CuCl2, ZnCl2) and of N-trityl-morpholine (Triphenmorph) were studied on two aquatic amphipod species, Gammarus pulex and Echinogammarus berilloni. Experiments were made up in eucalcic and oligocalcic waters for determining the LC50 at different exposure times. The order of toxicity was the same in eucalcic water with the two species: Triphenmorph greater than Cu2+ greater than Zn2+ greater than Ba2+. This order was the same in oligocalcic water with Echinogammarus berilloni; with Gammarus pulex, CuCl2 was more toxic than Triphenmorph.

Animals↗

PubMed1979

[Study of the enzymatic hydrolysis of a phosphonic ester using microcalorimetry].

A "Batch" microcalorimeter is used at 30 degrees C for the study of the hydrolysis of 4-nitro-phenylphenylphosphonate with a calf-intestinal phosphonate esterase, in a tris buffer, pH 8. The yield of enzymatic hydrolysis is estimated by spectrophotometric determination of the p--nitrophenol evolved; we have then calculated the apparent molar enthalph of the reaction. (delta Happ = -72,2 kj. mol-1). Phenylphosphonic acid, the second reaction product, is not transphosphonylated on tris. The second acidity of phenylphosphonic acid was studied at 30 degrees C by sodium hydroxide electrotitration (pKa2 = 7,13) and by "Flow" microcalorimetry (delta Hionization = 19,8 kj.mol-1). In the same manner at 30 degrees C, we measured the heat of ionization of p-nitrophenol (delta Hionization = 26,75 kj.mol-1). These findings allow a calculation for the actual heat of hydrolysis of 4-nitro-phenyl-phenylphosphonate (delta Hrho = -29,7 kj.mol-1).

Animals↗

PubMedDate not supplied

Analytical findings in a suicide involving sodium azide.

A 47-year-old laboratory assistant ingested approximately 9 g of sodium azide powder and died 4 h later at a hospital. A high-performance liquid chromatographic method using diode-array detection has been developed for the determination of an azide benzoyl derivative in blood (after a simple deproteinization) and in several tissues (after homogenization in a neutral buffer and deproteinization of the supernatant). The blood concentration in this case was lower than those previously published. The highest azide concentration was found in lung tissue. A complete toxicological screening revealed the presence of cyanide in blood, which has been previously reported twice, but for the first time, it was confirmed by mass spectrometry. Whether the production of cyanide in the presence of azide took place in vivo or postmortem remains unknown; the nature of the metabolic pathway involved also remains unknown.

Azides↗

PubMedDate not supplied

A screening procedure for the determination of 13 oral anticoagulants and rodenticides.

A technique for the simultaneous identification and quantitation of 13 hydroxycoumarin and indandione anticoagulant drugs and rodenticides from human serum by reversed-phase liquid chromatography with diode-array detection has been developed. High-performance liquid chromatography was performed using gradient elution with an acetonitrile and phosphate buffer on a Nucleosil ODS column. Ultraviolet spectra from 200 to 400 nm were recorded on-line during the analysis and compared with spectra stored in a library. For the spiked 2 mL of serum, acidic and alkaline liquid-liquid double extraction with diethylether-ether acetate (50:50, v/v) was conducted, and recoveries greater than 60% for most compounds were found. The detection limit was approximately 25 or 50 ng/mL for all components except for difethialone and fluindione, for which it was approximately 100 ng/mL. The standard calibration curves were linear from the detection limit to 5000 ng/mL. The within-run precision coefficient of variation (CV) was less than 10%, and the between-run precision CV was less than 20%.

Administration, Oral↗