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Biomedical subjects

J Barre

Publications and source records attributed to J Barre.

At least 19 recordsLinked to original sources
PubMed2004

Pharmacokinetic modelling of cefotaxime and desacetylcefotaxime--a population study in 25 elderly patients.

OBJECTIVE: To develop a pharmacostatistical model to simultaneously characterise the pharmacokinetics of cefotaxime and its main metabolite, desacetylcefotaxime, in elderly patients. METHODS: Cefotaxime, 1 g, was infused three times daily to 25 elderly patients, 66-93 years old. Cefotaxime and desacetylcefotaxime plasma concentrations (289 and 304 samples, respectively), along with demographic and physiological characteristics, were analysed using a population approach. RESULTS: Cefotaxime pharmacokinetics was best described by a two-compartment open model in which desacetylcefotaxime was produced from the central compartment. The final parameter estimates were derived from simultaneous fit of parent/metabolite data. Cefotaxime clearance, mean 5.5 l/h, was positively influenced by body weight and serum protein concentration and negatively influenced by serum creatinine and age. In contrast, desacetylcefotaxime elimination was only decreased by age. The mean terminal half-lives of cefotaxime and desacetylcefotaxime were 1.7 h and 2.6 h, respectively. The stability and predictive performance of the final population pharmacokinetic model was assessed using 200 bootstrap samples of the original data. CONCLUSION: Cefotaxime and desacetylcefotaxime elimination decreased with increasing age above 60 years. This decreased elimination was related to individual characteristics that are typically related to renal function.

Aged↗
PubMed1999

Prevention of deep vein thrombosis after hip replacement--comparison between two low-molecular heparins, tinzaparin and enoxaparin.

Consecutive patients undergoing total hip replacement in 43 centres were randomly assigned to receive blindly either enoxaparin (40 mg) or tinzaparin (4,500 anti-Factor IU Xa), as once daily subcutaneous injections. The first injection was administered 12 h preoperatively. Efficacy was assessed by bilateral venography performed 12-14 days postoperatively. Efficacy and safety were blindly and centrally adjudicated. Among the 499 patients included, 440 had a venogram. The total incidence of DVTs was 44 (20.1%) of the 219 patients of the enoxaparin group and 48 (21.7%) of the 221 patients of the tinzaparin group. The upper limit of the 80% confidence interval of the difference between the two treatment groups was less than 5.0%. Therefore according to the protocol's specifications equivalence was shown. Proximal DVTs occurred in 10.5% of the enoxaparin group (23 patients) and in 9.5% (21 patients) of the tinzaparin group. No overt major bleeding was observed. One patient in the enoxaparin group developed severe thrombocytopenia and died. The LMWH tinzaparin appears clinically to be as effective and safe as enoxaparin in the prophylaxis of deep vein thrombosis after total hip replacement, at the doses used and under the conditions of this study.

Adult↗
PubMed1998

[Blood volume changes caused by position under general anesthesia].

The cardiovascular changes in response to general anaesthesia are related to several interacting mechanisms. In addition to the intrinsic effects of anaesthetic agents on the heart and vessels which depress the physiological mechanisms of adaptation, the additive independent effects of posture and mechanical ventilation on intravascular blood volume have to be considered. Physiopathologic studies show that the ultimate related mechanism is the decrease of venous return to the heart. The major effect of posture is the change in the distribution of the blood volume, as the posture modifies the influence of gravity in addition to direct vascular compression and stretching. The deterioration of the cardiac venous return results in dramatic or insidious clinical consequences which lead finally to a low cardiac output. As cardiac function is not a limiting factor of output, any decrease of blood pressure in a patient with a healthy heart must be considered as an hypovolaemic state due to an abnormal contents to container ratio, and must be managed as such.

Anesthesia, General↗
PubMed1997

Clinical features and echocardiography of embolism during cemented hip arthroplasty.

PURPOSE: In previous studies the degree of embolization detected by transoesophageal echocardiography (TEE) during cemented total hip arthroplasty (THA) did not correlate with changes in haemodynamic variables nor did it result in persistent ventilation-perfusion mismatching. The aim of this study was to record evidence of embolism and to relate the findings to demographic data and the subsequent clinical course of the patients during THA. METHOD: Forty-eight patients scheduled to undergo elective cemented THA during general anaesthesia were monitored. A TEE probe was inserted with special attention to the right atrium (RA), the right ventricle (RV) Haemodynamic (heart rate, arterial blood pressure, central venous pressure) and blood-gas variables were measured repeatedly during the operative procedure (after induction, placement of the acetabular component, placement of the femoral component, relocation of the hip joint). Grading of venous embolism at these times was based on the size of particles detected by TEE (three-minutes video segments of each periods) and correlated with demographic, haemodynamic and blood-gas data. RESULTS: The TEE monitoring revealed showers of echogenic material traversing the RA and RV in all but one patients during reaming and cementing of the acetabular and femoral components, and during relocation of the hip joint. No correlation was observed between frequency or size of embolic particles and demographic or blood-gas and haemodynamic variables studied at the same times. CONCLUSION: This study failed to show any clinical impact of TEE detected emboli during cemented THA.

Aged↗
PubMed1997

Trimetazidine does not modify blood levels and immunosuppressant effects of cyclosporine A in renal allograft recipients.

AIMS: In renal allograft recipients, trimetazidine (Vastarel) was proposed to be associated with the classic immunosuppressant treatments because it displays anti-ischaemic effects which may protect against cyclosporine A nephrotoxicity. The objective of this work was to assess the possibility of coadministering cyclosporin A, Sandimmun, and trimetazidine. METHODS: Twelve renal transplant patients were selected on the basis of the stability of their cyclosporine A blood concentrations for the previous 3 months. They received trimetazidine, 40 mg twice daily orally for 5 days. Other coadministered drugs were kept unchanged during the study. Before and after trimetazidine administration, cyclosporine A blood concentrations, plasma interleukin-2 and soluble interleukin-2 receptor levels were measured. RESULTS: The data showed that neither cyclosporin A blood pharmacokinetic parameters, Cmax, tmax, AUC, nor the concentrations of interleukin-2 and soluble interleukin-2 receptors were significantly modified. CONCLUSIONS: Therefore, it was suggested that trimetazidine may be coadministered with cyclosporine A without cyclosporine A dosage adjustment.

Adult↗
PubMed1997

Low molecular weight heparin associated with spinal anaesthesia and gradual compression stockings in total hip replacement surgery. Arar Study Group.

The benefit/risk ratio of administering heparin during spinal anaesthesia in patients undergoing total hip replacement (THR) has not been studied widely. We conducted a prospective, randomized, double-blind study to compare low molecular weight heparin (LMWH) for 10 days and placebo in patients undergoing THR performed under spinal anaesthesia associated with gradual compression stockings. Efficacy was assessed by systematic bilateral ascending venography on day 10 +/- 2 in a sequential analysis. Among the 170 patients enrolled, data were available in 153 patients. In the LMWH group (n = 78) the total incidence of deep vein thrombosis (DVT) was 14.1% compared with 37.3% in the placebo group (n = 75) (P = 0.0016). No gross neurological sequelae were observed during the study. This study showed that the addition of LMWH in patients undergoing THR under spinal anaesthesia and wearing gradual compression stockings significantly decreased the incidence of venogram-proved DVT.

Adult↗
PubMed1997

Bactericidal activity against intermediately cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with bacterial meningitis treated with high doses of cefotaxime and vancomycin.

Cerebrospinal fluid (CSF) was taken from 19 children with bacterial meningitis treated with cefotaxime (300 mg/kg of body weight/day) and vancomycin (60 mg/kg/day). Median levels of drugs in CSF were smaller than expected, as follows: 4.4 microg/ml for cefotaxime, 3.2 microg/ml for desacetylcefotaxime, and 1.7 microg/ml for vancomycin. The median CSF bactericidal titer against an intermediately cefotaxime-resistant pneumococcus was 1:4. Our data suggest at least an additive interaction between the drugs used in this study.

Adolescent↗
PubMed1997

[Embolism and intramedullary femoral surgery].

All intramedullary femoral surgery entails embolic phenomena which explain peroperative collapses formally known as bone cement implantation syndrome, as well as perioperative fat embolism syndromes. Locally, the bigger the cavity is, the higher the number of accidents: 2.5-5 per cent for GUEPAR hinged-knee prosthesis, 1.75 per cent for total hip arthroplasty with long stem, and 0.1 per cent during classic THA with cement limited to the metaphysis. Anomalies in bone vascularization also increase risk: 10.5-13 per cent during prophylactic nailing for shaft metastases, 1-11.5 per cent during hemiarthroplasty cemented in osteoporotic bone of femoral neck fractures, and only 0.1 per cent during THA implanted because of arthrosis. Not only cement, but also rods, reamers, nails, implants, ultrasonic tool for cement extraction, increase the pressure inside the cavity. Methylmethacrylate is no longer the only incriminated factor, even if it is responsible for a major part of the compressive load. The intensity and duration of the pressure are correlated with the number of embolic phenomena and with measured cardiopulmonary parameters. The intracavity fat content is expelled (an empty cavity, as in THA revision, does not lead to embolic phenomena). Then filters through the intraosseous veins whose diameter limit the size of the extruded embolic phenomena. The ultrasonography of the inferior vena cava shows innumerable fine particles and thrombi which are already organized under the influence of procoagulant factors released from the operative shield and which remain crumbly. These emboli cross the cardiac cavities. Transesophageal echocardiography (TEE), of recent use, does quantify the amount of right atrial filling, duration of echogenesis and size of particles: the result is higher in patients who underwent cemented versus noncemented THA: however the embolism score is no an indicator of seriousness because it is not correlated with cardiorespiratory manifestations; TEE shows only one fourth of the patent foramen ovale, whereas the atrial septal defect is surely one of the most efficient systemic invasion mechanisms to produce perioperative fat embolism. Lung response is most often asymptomatic, even if all patients undergoing intramedullary surgery display an increase in pulmonary vascular resistance which is managed by the right heart only, as well as pulmonary (and sometimes systemic) microvascular fat obstruction. Common operating room monitoring procedures do not detect successive embolic phenomena before they cause pulmonary arterial hypertension which then has repercussions on the left heart and in turn causes peroperative hemodynamic accidents. Only pulmonary arterial pressure measurement with a Swan-Ganz catheter gives early and durable signs of an intolerance to embolic load. Preventive treatment is surgical as there is an inverse relation between embolic marrow and marrow eliminated by large volume washes (which is often more effective than draining). Cement indications in older patients as well as the choice of fixation techniques in femoral fractures must take into account the cardio-pulmonary condition of the patient. Resuscitation procedures dealing with these complications end in the patient's death in half of the cases.

Animals↗
PubMed1995

Pharmacokinetics and pharmacodynamics of rocuronium at the vocal cords and the adductor pollicis in humans.

The pharmacokinetic-pharmacodynamic relationship of rocuronium at the laryngeal adductor muscles and the adductor pollicis was determined in eight patients during general anesthesia. Rocuronium was administered as an infusion at a rate of 100 micrograms.kg-1.min-1 over 5 minutes. The half-life of transport between plasma and biophase (effect compartment) was significantly shorter at the adductor laryngeal muscles (2.7 +/- 0.6 minutes, mean +/- SD) than at the adductor pollicis (4.4 +/- 1.5 minutes, p = 0.003). The concentration in the effect compartment producing 50% of the maximum effect was significantly greater at the adductor laryngeal muscles (1424 +/- 148 micrograms.L-1) than at the adductor pollicis (823 +/- 157 micrograms.L-1, p = 0.0001). The shorter onset of neuromuscular blockade at the laryngeal muscles than at the adductor pollicis may be explained by a faster transfer rate at the laryngeal adductor muscles neuromuscular junction than at the adductor pollicis neuromuscular junction.

Adult↗
PubMed1994

[Hemorheologic changes in preoperative hemodilution during total hip replacement. Randomized study comparing hydroxyethyl starch 200,000/0.62 (HES) and a dextran 60,000].

Hemodilution can be used to save blood transfusion during total hip replacement. We have carried out a randomized study to compare the hemorheological effects of two plasma substitutes: a hydroxyethylstarch 200,000/0.62 versus a dextran 60,000. Twenty-two patients were hemodiluted with 20 mk/kg of either substitute, just after the spinal anesthesia. Whereas the hematocrit have fallen by 30% in the two groups, significant differences are observed about hemorheological parameters. The plasma viscosity express a greater increase at hour 4 in the dextran group. The whole blood viscosities are more increased in the dextran group at hour 4 and 24. The erythrocyte aggregation is decreased in the HES group at hour 4 and 24, but is increased in the dextran group. The fibrinogen is more increased in the dextran group at day 7. In spite of similar hemodilutions, the two substitutes express different hemorheological effects with a favourable role of HES on erythrocyte aggregation and blood viscosities. This can improve the microcirculation and decrease the activation of the endothelial cells, reducing the inflammatory reaction.

Adult↗
PubMed1994

Linear pharmacokinetics of a new inotropic agent.

The dose-dependent pharmacokinetics of N,N'-dicyclopropyl-methyl-piperazine- dichlorhydrate (Ino 2628 CZ, CAS 82909-97-5), a new inotropic compound, was studied after 4 intravenous infusions in 3 subjects and 4 orally administered doses in 6 subjects. Plasma and urine levels were determined over 72 h. The results show that the pharmacokinetics of Ino 2628 CZ was dose proportional over the intravenous and oral dose range of 100 to 400 mg.

Administration, Oral↗
PubMed1993

Clinical pharmacology of oxicams: new insights into the mechanisms of their dose-dependent toxicity.

Six oxicams, sudoxicam, isoxicam, piroxicam, tenoxicam, meloxicam and lornoxicam, were compared in an attempt to understand why, despite close chemical structures, two of them were associated with an increased risk of toxicity in patients. Different factors have been revealed which may explain these differences. A weak association constant to human serum albumin (HSA), together with a high plasma concentration, favours a rapid increase in unbound concentration (Cu) when total plasma concentration rises (peak of absorption). Pathological states may enhance this increase when both HSA plasma concentration is decreased and free fatty acid concentrations are increased. However, the main cause of toxicity may be the existence in some subjects of HSA natural mutants whose ability to bind oxicams is markedly lower than normal.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Application of a pharmacokinetic model with multiple enterohepatic cycles to a new inotropic drug after infusion and oral administration.

A pharmacokinetic model with multiple, unequal, enterohepatic recirculations was developed to fit the experimental data of a new inotropic drug after intravenous infusion and oral administration. Optimized model parameters were used to derive theoretical values of the area under the curves of concentration versus time that were in good agreement with the experimental values.

Administration, Oral↗
PubMed1992

Plasma assay of salbutamol by means of high-performance liquid chromatography with amperometric determination using a loop column for injection of plasma extracts. Application to the evaluation of subcutaneous administration of salbutamol.

An isocratic high-performance liquid chromatography method with amperometric detection for the assay of plasma salbutamol is described. The plasma extract is injected into the chromatographic system via a loop column. This insures the purification of the injected extracts and allows a simple and rapid liquid-solid extraction procedure. The good reliability, as shown by the low limit of detection (0.5 ng/ml) and a precision ranging between 5 and 10%, has permitted the investigation of a new mode of administration of salbutamol using a portable subcutaneous infusion pump. Our results show that subcutaneous administration yields plasma levels comparable with those obtained after usual intravenous doses.

Albuterol↗
PubMed1992

[Respective role of mifepristone (RU486) binding to blood and tissue proteins in its quantitative distribution in the body].

In plasma, mifepristone (RU486)-alpha 1-glycoprotein acid (AGP) interaction follows a quickly saturable process within the range of therapeutic concentrations. The high affinity to AGP, Kap = 8 x 10(6) M-1, suggests that the tissue distribution of the drug is possibly impaired. Checking this hypothesis was done by simulating its body distribution between plasma proteins and tissues. Two methods were used. The first was to calculate the number of available binding sites in both plasma (Np) and tissues (NT), to measure the relevant association constants Kap and KaT, and to consider that mifepristone partitioned according to their ratios, expressed as [NpKap]/[NpKap + NTKaT] for the plasma and [NTKaT]/ NpKap + NTKaT] for the tissues. The second method used equations relating the apparent volume of distribution and the plasma unbound fraction of mifepristone with volumes of physiologic spaces to calculate the percentage of drug located in plasma, extracellular and intracellular fluids. The results yielded by the two methods are close. They show that with AGP levels within a normal range (18.4 microM), only 18% of mifepristone is bound to AGP and the remaining part 82% is located in tissues. By contrast, when AGP level dramatically increases (300 microM) most of the dose (77%) is retained in plasma. These results suggested that when AGP concentration increases, the efficacy of therapeutic concentration of mifepristone may be partially decreased if only the unbound fraction of this synthetic hormone were biologically active.

Dose-Response Relationship, Drug↗
PubMed1992

[A comparative microbiological and pharmacokinetic activity of vancomycin and teicoplanin].

Vancomycin and teicoplanin are two commercially available glycopeptide antibiotics. They have identical spectra of activity and similar mechanisms of action, and both are complex molecules. In vitro, vancomycin is more active against coagulase-negative staphylococci, while teicoplanin is more active against enterococci and pneumococci. The activity of the two antibiotics against Staphylococcus aureus is similar. The serum pharmacokinetics of vancomycin and teicoplanin are highly different, teicoplanin having a longer elimination half-life (40 hours versus 6-8 hours for vancomycin), but a higher degree of protein binding (90% versus 55%). We compared the two antibiotics on the basis of their inhibitory quotient kinetics, using the MIC90 values for the above bacterial species as the microbiological parameters, and the total and free (non-protein bound) serum concentrations as the pharmacokinetic parameters. The inhibitory quotient kinetics of vancomycin were always more favorable in terms of the free concentrations, even against those bacteria for which the teicoplanin MIC was lower.

Dose-Response Relationship, Drug↗