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The ionization effect on both the evolution and internal structure of a blast wave (BW) is determined in laboratory conditions. In a first step, the Rankine–Hugoniot equations describing the structure of the shock front together with the Saha equation modeling ionization are solved analytically in a consistent way for the conditions of a cold initial atomic hydrogen gas. In a second step, a simplified approach is used by introducing an effective adiabatic index γ * that takes into account ionization arising at the shock front. Finally, γ * is used as input data in the self-similar model derived formerly by Barenblatt to describe the structure and the dynamics of the ionizing BW. For the typical laboratory conditions of blast wave experiments, ionization achieves a hydrogen gas compression up to about 11 times at the shock front of the blast wave where a thin and dense shell forms. For such a compression, the value of the effective adiabatic index is γ * ≃ 1.2 leading to a self-similar evolution of the BW where its radius R(t) varies according to R ( t ) ∝ t α * with α * ≃ 0.33. This value of α * is lower than the adiabatic expansion stage α = 2 / 5, where the total energy of the BW is conserved. Thus, ionization is found to act as a cooling effect at the shock front where a fraction of kinetic energy is absorbed to ionize the gas.

Goncharov's [Phys. Rev. Lett. 88, 134502 (2002)0031-900710.1103/PhysRevLett.88.134502] nonlinear model of a single-mode Rayleigh-Taylor instability (RTI) is investigated for a partially ionized plasma in a predominantly neutral background. Terminal bubble and spike velocities are derived from the nonlinear equations in the case where the RTI dynamics is dominated by collisions between neutrals and ions. Direct numerical simulations are used to justify the use of Goncharov's model in this regime and observe its limitations.

The self-similar study of cooling blast waves (BWs) is performed for the case of a homogeneous self-similar cooling of the gas. This analysis is crucial to better understand its internal structure and global evolution when the BW loses a significant amount of energy due to cooling processes. The evolution of the shock front radius Rsh follows the law Rsh(t) ∝ tα where the decelerating parameter α covers the range 1/4 ≤ α ≤ 2/5 depending on the magnitude of the cooling rate. When the cooling is negligible, α = 2/5, and we recover the analytical solution of Sedov-Taylor (ST) where the total BW energy is conserved. For the internal structure of the cooling BW, we demonstrate that there exist two types of solutions. The first type is the ST-type solution, which is smooth until the center of the BW and only exists for 1/4 < α′ ≤ α ≤ 2/5, where α′ is a specific value of α. This special solution is determined through an eigenvalue problem. The second type is a shell-type solution where a thin cooled shell is bounded by a contact discontinuity separating the shell from a hot rarefied interior bubble where the pressure is homogeneous. The shell becomes thinner and denser when the cooling rate increases. For a strong enough cooling rate, the density inside the shell can diverge at the contact discontinuity while the temperature goes to zero.

In naturally fractured carbonate reservoirs, Gas Oil Gravity Drainage processes (GOGD) are successfully implemented but oil recovery is limited by a slow kinetics. However a gas EOR process represents a promising alternative to boost this oil production rate. Nevertheless the design of this process should address several technical challenges: the typically unfavorable wettability of the matrix (intermediate to strongly oil-wet), the densely connected fracture network and the high contrast of fracture-to-matrix permeability. We propose here the injection of an advanced EOR foam with reduced interfacial tensions. The foam flow in the fracture creates an important viscous drive by imposing a pressure gradient, thus enhancing the oil recovery dynamics compared to GOGD. Besides, the reduced interfacial tension (IFT) between crude oil and aqueous phase allows the aqueous phase to enter the matrix despite the unfavorable wettability. In this paper, we demonstrate that a balance exist between IFT and foam strength performances to optimize the process. Three foam formulations are optimized with very different profiles in terms of IFT and foam performances. For their design, priority is given either to ultra-low IFT values (0.001mN/m) or to a strong foam with larger IFT (0.15mN/m) or to a balance between the two first formulations (0.03mN/m). These formulations are compared in vials, sandpack and coreflood experiments (fractured cores). Foams are evidenced as intrinsically less stable in ultra-low IFT conditions: foam stability (in vials) and apparent viscosity (in porous media) in contact with oil are respectively enhanced by a factor 30 and by two decades when IFT rises from 0.001 to 0.1mN/m. Based on sandpack and coreflood experiments, we recommend an IFT of 0.1 to 0.01mN/m as a balance between the viscous drive in fracture and an efficient aqueous phase imbibition in the oil-wet matrix. Simulation work supports this experimental conclusion: the common target of IFT of the order of 0.001 mN/m determined by capillary desaturation curves in SP flooding can be revised to a higher IFT, which is can be deduced from the wettability of the reservoir. To ensure an accelerated oil recovery in naturally fractured carbonate reservoirs, we recommend the design of a low-IFT foam formulation with revised IFT performances compared to a classical Surfactant-Polymer process. This article gives the target formulation parameters which arise from the mechanisms at play (viscous drive and imbibition in oil-wet matrix), and are realistically achieved with industrial surfactants.

the date of receipt and acceptance should be inserted later Abstract. The Rayleigh-Taylor instability plays an important role in the dynamics of several astronomical objects, in particular, in supernovae (SN) evolution. In this paper we develop an analytical approach to study the stability analysis of spheric al expansion of the SN ejecta by using a special transformation in the co-moving coordinate frame. We first study a non-stati onary spherical expansion of a gas shell under the pressure of a central source. Then we analyze its stability with respect to a n o radial, non spherically symmetric perturbation of the of the shell. We consider the case where the polytropic constant of the SN shell isγ = 5/3 and we examine the evolution of a arbitrary shell perturbation. The dispersion relation is derived. The growth rate of the perturbation is found and its temporal and spatial evolution is discussed. The stability domain depends on the ejecta shell thickness, its acceleration, and the perturbation wavelen gth.

Partial modeling of the hydrodynamic evolution of the supernovae is one of the prominent applications of laboratory astrophysics. In particular the role of Rayleigh–Taylor instability (RTI) in supernova evolution needs to be explained. In this paper we analyze the compressibility effects on the RTI in the linear regime. We compare the compressible isothermal and stratified incompressible RTI growth rates and analyze the vorticity generation at the interface. We show that for several configurations the effect of compressibility can be significant in supernovae remnants.

A selective and sensitive high-performance liquid chromatographic (HPLC) method has been developed and validated for the determination of six human immunodeficiency virus (HIV)-protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) and two non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine) in a single run. This involve a simple liquid-solid extraction on OASIS® HLB column in the presence of an internal standard (prazepam). Separation is achieved on a Xterra®, C18 (150 × 3.9 mm I. D.) column with a mobile phase consisting of acetonitrile and 3-(cyclohexylamino)-1-propanesulfonic acid (CAPS) buffer pH 10.5, (37 : 63, v/v) delivered isocratically. A sequential ultraviolet detection (5 minutes sequence set at 320 nm for nevirapine acquisition and 55 minutes at 210 nm for other durgs and internal standard) is performed. The method is linear over the specific ranges investigated. Precision and accuracy at four concentrations are respectively less than 13.6% and 9.1% for intraday assays and less than 4.2% and 5.9% for interday assays. This method is suitable for therapeutic drug monitoring purpose and routinely used in our laboratory.

The interaction of the mixing zone between two gases of different densities with compression waves and shock waves has been investigated. The characteristics of the mixing zone in which the Rayleigh–Taylor instability is developing have been analyzed. The evolution of the mixing zone volume and mass during the accelerated motion has been defined. A qualitative distinction in the evolution of the mixing zone under the influence of a continuous deceleration resulting from the interaction with the reflected compression wave—shockless deceleration—is revealed as compared to deceleration that is accompanied by appearance of a shock wave moving through the mixing zone—shock-induced deceleration.

Intranasal midazolam was studied in two series of piglets: series 1, n = 20 (18 ± 3 kg), a randomized double blind pharmacodynamic study to compare doses of 0.2 mg/kg and 0.4 mg/kg; series 2, n = 9 (42 ± 8 kg), a pharmacokinetic study with a 0.4 mg/kg dose administered either intravenously (i.v.) or intranasally (i.n.) in a cross-over protocol with a one-week wash-out period between each. In series 1, midazolam caused significant anxiolysis and sedation within 3 to 4 min, without a significant difference between 0.2 and 0.4 mg/kg doses for any of the studied parameters. In series 2, after intranasal midazolam administration of 0.4 mg/kg, plasma concentrations attained a maximum (Cmax) of 0.13 ± 0.04 mg/l at 5 min (median Tmax) and remained higher than 0.04 mg/l until 60 min. The bioavailability factor (F) in this study was F = 0.64 ± 0.17 by the intranasal route. The terminal half-life (T1/2 λz) = 145 ± 138 min was comparable with the i.v. administration half-life (158 ± 127 min). In conclusion, optimal intranasal midazolam dose in piglets was 0.2 mg/kg, which procures rapid and reliable sedation, adapted to laboratory piglets.

A sensitive and rapid high-performance liquid chromato-graphic method using UV detection, has been developed for the analysis of meropenem in plasma. This involved a single liquid-solid extraction on Isolute C18-EC column in the presence of an internal standard (ceftazidime). Analysis was performed by isocratic elution with a mobile phase consisting of 0.01 M acetate buffer pH 4.8 containing 15% (v/v) methanol, with UV detection at 296 nm. The limit of quantitation of the assay was 0.125 mg/L. The method was applied to a pharmacokinetic study in rats receiving 100 mg/kg by IV route with a good accuracy (94–101%) and precision (less than 13%).

It is shown that ``Liouville's theorem'' on integrability still holds in the case of time-dependent Hamiltonian systems; when they have $n$ independent, possibly time-dependent, invariants the solution can be found with quadratures and no chaos can take place. This is applied to three important problems describing the motion of a particle in an electromagnetic field. The first is the motion of a charged particle in a homogeneous constant magnetic field and a transverse circularly polarized homogeneous electric field. In the second application the electric field is replaced by a standing electromagnetic wave. The third concerns an oscillator with a quadratic nonlinearity in the force.

The Rayleigh-Taylor instability (RTI) plays an important role in the dynamics of several astronomical objects, in particular, in supernovae (SN) evolution. In this paper we develop an analytical approach for the stability analysis of spherical expansion of the SN ejecta. We study a non-stationary spherical expansion of a gas shell under the pressure of a central source. Then we analyze its stability with respect to angular perturbations. The growth rate is found and the temporal and spatial evolution of the perturbed shell is discussed. Finally, we propose a specific laser experiment to test our model.

International audience; In the framework of the Laboratory Astrophysics, we present new radiative shocks experiments performed using the LULI2000 facility. A strong shock is driven in a multi-layered solid target (CH-Ti-CH) which accelerates into a gas cell (˜ 60 km/s) filled with Xenon at low pressure (0.1 - 0.3 bar) and produces a radiative supercritical shock [4, 8]. A low power laser beam (8 ns - 532 nm) probes the Xenon gas in the transverse direction and is injected into a VISAR and on two optical framing cameras (GOI). These diagnostics allow to determine electron density variation, to measure both precursor and shock velocities along the shock propagation axis [3, 5] as well as the 2D shape of the shock. On rear side, the light emitted from the shocked Xenon is imaged onto the slit of a streak camera. An absolute calibration of the optical system allows to determine the brightness temperature [8]. Data were obtained for different laser intensities and gas pressures. Two VISARs on rear side allowed an accurate measurement of the shock conditions in the pusher before the breakout in the Xenon. Comparison between 1D (MULTI) and 2D (DUED [1, 2]) radiative hydrodynamic codes and measured quantities (shock velocity, shape, radial expansion, and temperature as well as precursor velocity and precursor electron density) are presented.

The PT is applied to the general second- and third-order ordinary differential equations invariant under the two symmetries associated with time translation and rescaling in order to investigate their solvability and global integrability. The effect of the two symmetries on the compatibility conditions is determined and we show that, generally, these conditions are automatically a consequence of the resonance condition. Use is made of truncated Laurent series both in ascending and descending powers. As an example, the case of the generalized Chazy equation is presented.

This paper presents a high density pressure measurement ribbon used to characterize air-flow on a shape. The system is made of 128 15-bits pressure sensors thermally compensated by 10 bits temperature sensors. The MEMS pressure sensor capacitance variations are converted into digital thanks to a second order switched capacitors sigma-delta converter. An innovative serial-bit sliding window FIR filter allows asynchronous data transfer on the 8MHz SPI like bus with limited time response (

We use analytic self-similar solutions of both the linear and non-linear diffusion equation to determine the behavior of a heat conducting system experiencing a time-dependent energy production. Supposing a power law evolution of the system parameters, we calculate the corresponding exponents to describe the temporal behavior of the system. In the non-linear case, we are able to introduce a variation of both the coefficient of diffusion and the amplitude of the heat source. The analytic solutions are checked numerically. These results can be considered, for example, as the basis for further developments on the non-linear behavior of supercritical fluids in a microgravity environment, e.g. the “Piston Effect” (M. Bonetti et al., Phys. Rev. E 49 (1994) 4779) or the “Jet Instability” (D. Beysens et al., Near-critical Fluids in Space, in: Lectures on Thermodynamics and Statistical Mechanics, M. Costas et al., eds. (World Scientific, Singapore, 1994) p. 88).

The in vivo pharmacokinetic interaction between two selective serotonin reuptake inhibitors (SSRI) (fluvoxamine, fluoxetine) and tricyclic antidepressants (TCAs) (amitriptyline, clomipramine) or neuroleptics (haloperidol, cyamemazine, levomepromazine, propericiazine) was assessed in 29 in-patients. They were phenotyped twice with dextromethorphan and mephenytoin: first in steady state conditions while under treatment with TCAs or neuroleptics; and also 10 days after an associated treatment with fluvoxamine (150 mg day(-1)) or fluoxetine (20 mg day(-1)). A clear and statistically significant increase in the mean urinary metabolic ratio (MR) of dextromethorphan/dextrorphan and in the mean mephenytoin S/R ratio (S/R) was seen with the fluvoxamine and fluoxetine treatment. The mean MR increased from 0.13 to 0.27 (P

In this article, the stationary Kuramoto–Sivashinsky (KS) equation is studied. It is shown, first, that this equation can be transformed into a one‐dimensional Hamiltonian system describing the motion of a particle in a time‐dependent potential. Second, working with this formalism and coming back, then, to the initial KS equation, a subset of initial conditions is derived for which the corresponding solutions u(x) will behave like the dominant pole 120/(x−x0)3, deduced from the Painleve analysis, and will explode in a finite ‘‘time.’’ Finally, special attention is given to the well‐known Kuramoto–Tsuzuki solution and it is shown that provided the independent variable x is initialized in a specified domain, this solution explodes also like 120/(x−x0)3.

In this paper, a theoretical analysis of the physical processes taking place in the electrothermal gun is presented. In a first step, using the basic conservation equations (energy, mass, charge) integrated over the whole time of the discharge, scaling laws are derived. These laws provide the temperature, the mass, the resistance of the plasma and the current going through it, as functions of the stored electrical energy. In a second step, a 0D time-dependent model is presented. This model takes into account the evolution of the complete system consisting of the electrical source, the plasma burner and the motion of the projectile. Special attention is given to the ablation phenomena and a microscopic description which differs from prior publications is derived. Finally, comparisons with experiments are given and good agreements are obtained. >

A sensitive and rapid High-performance liquid chromatographic method using U. V. detection, has been developed for the analysis of thalidomide in plasma. This involved a single liquid-solid extraction on Extra-Sep-C8 column in the presence of an internal standard (ciprofloxacin). Analysis was performed by isocratic elution with a mobile phase consisted of 0.01 M aqueous potassium dihydrogen phosphate containing 21% (V/V) acetonitrile and 4.5 mM Heptane sulfonic acid, adjusted to pH 2.3, with U. V detection at 295 nm. The limit of sensitivity of the assay was 0.06 mg/l. The method was applied to a pharmacokinetic study (50 to 100 mg) in patients with erythema nodusum leprosum (ENL) with a good accuracy (96–111%) and precision (less than 5.8%).

In this paper, we look for first integralsI(q;p;t) of time-dependent one-dimensional HamiltoniansH(q;p;t). We first present a formalism based on the use of canonical transformations, and it is seen thatI(q;p;t) can always be written in terms of two variablesI=P(u;v), whereu andv are functions ofq, p andt, without loss of generality. Moreover, it is shown that any Hamiltonian with first integralI(q;p;t) can be made autonomous in the space (u, v, T), whereT is a new time. On the other hand, the cases of a particle moving classically and relativistically in a time-dependent potentialV(q;t) are studied. In both cases, completely integrable potentials, together with the corresponding first integrals, are derived.

In this paper, first integrals of one‐dimensional time‐dependent relativistic Hamiltonians are looked for. In a first step, potentials for which the corresponding motion equations are completely integrable are found. In a second step, a more realistic potential described by the time‐dependent relativistic harmonic oscillator is studied. It appears that it is not analytically integrable. However its asymptotic evolution systematically converges towards a classical evolution for which we can exhibit a first integral.

The Hamiltonian formalism for a two-dimensional system of ODE possessing an invariant of the motion not containing the time explicitly has suggested a method for the search of first integrals. Applied to the quadratic system it leads to the finding of two phase space configurations.

A simple and reliable isocratic reversed-phase HPLC method for the determination of phenylacetic acid (PAA) in urine is described. After acid hydrolysis of its glutaminoconjugate, phenylacetic acid is extracted by diethylether; chromatography is followed by UV detection at 210 nm. This rapid method is quite specific and sufficiently sensitive. We found satisfactory linearity up to 200 mg/1 PAA urinary concentrations. Within-day and between-day assays showed variation coefficients below 10 %. Twenty-four hour urinary excretion of PAA might therefore be easily and routinely measured; it could represent a noninvasive and suitable biological marker in psychiatry.

In this paper, we study self-similar solutions, and their linear stability as well, describing the flow within a spherical shell with finite thickness, expanding according to a power law of time, t q , where q>0. The shell propagates in a medium with initially uniform density and it is bounded by a strong shock wave at its outer border while the inner face is submitted to a time-dependent uniform pressure. For q=2/5, the well-known Sedov–Taylor solution is recovered. In addition, although both accelerated and decelerated shells can be unstable against dynamic perturbations, they exhibit highly different behaviors. Finally, the dispersion relation derived earlier by Vishniac (Vishniac, E.T. in Astrophys. J. 274:152, 1983) for an infinitely thin shell is obtained in the limit of an isothermal shock wave.

A sensitive high-performance liquid chromatographic method, using electrochemical detection, has been developed for the analysis of both imipramine and desipramine in plasma. This involved many n-hexane-isoamyl alcohol extractions, in the presence of an internal standard (trimipramine). Analysis was performed by isocratic elution with 27 % 0.01M potassium dihydrogen phosphate, 40 % acetonitrile, 33 % methanol, with the pH adjusted to 9, on a Nucleosil 5 μm, CN column, with electrochemical detection at + 0.9 Volt. The limit of sensitivity of the assay was 1.0 ng/ml. The method was applied to a single dose (7 5 mg) pharmacokinetic study of imipramine, in healthy volunteers, with a good accuracy (95-105 %) and precision (less than 11.5 %).

The effect of time of administration on excretion of two brush border enzymes--alanine aminopeptidase (AAP) and gamma-glutamyl transferase (gamma GT), and a lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG) with a single high dose of vancomycin, gentamicin or a combination of vancomycin and gentamicin was studied in male Wistar rats and compared with elimination of a control group. The rats received vancomycin intraperitoneally (200 mg.kg-1), gentamicin intramuscularly (100 mg.kg-1) or the combination of the drugs by the same route. A control group received isotonic NaCl solution. The four groups of animals received a single injection at 8 a.m., 2 p.m., 8 p.m., and 2 a.m. and urine excretion values for AAP, gamma GT and NAG were determined 24 hr later. The results show that the nephrotoxicity of gentamicin + vancomycin is greater than that observed with gentamicin, which again is greater than that observed with vancomycin. Furthermore, circadian variations in renal toxicity were observed, the least occurring at 8 a.m.

In the field of CO2 storage, one important goal is to be able to prove that the injected CO2 is safely stored, and that no leak is occurring. Time-lapse seismic is one of the most powerful tools available for this purpose. However, it is generally used in

A rapid isocratic reversed-phase HPLC method for the determination of the major component of teicoplanin in plasma is described. By using solid phase extraction C18 and UV detection at 240 nm, this method is specific, and sufficiently sensitive. We found a good linearity over the range: 5 – 40 mg/1 of teicoplanin plasma concentrations. The coefficients of variation did not exceed 5.4% both within-day and between-day assays. With the small plasma sample required for the analysis (250 μl) and the good accuracy, this rapid procedure appears to be suitable for the therapeutic drug monitoring.

International audience; Dedicated laboratory astrophysics experiments have been developed at LULI in the last few years. First, a high velocity (70 km/s) radiative shock has been generated in a xenon filled gas cell. We observed a clear radiative precursor, measure the shock temperature time evolution in the xenon. Results show the importance of 2D radiative losses. Second, we developed specific targets designs in order to generate high Mach number plasma jets. The two schemes tested are presented and discussed.

Summary form only given. Radiative shocks occur in many high-energy density explosions, but prove difficult to create in laboratory experiments or to fully model with astrophysical codes. Here we describe an experiment significant to astrophysical shocks, which produces a driven, quasi-planar radiative shock in xenon gas at 6 mg/cc. A thin, low-Z disk is driven into a cylindrical volume of xenon gas via laser ablation pressure. This impact creates a shock in xenon, after which the disk travels behind the shock providing a continuing pressure source. With average shock speeds above 100 km/sec, this shock can radiate away energy just behind the shock front, creating a thin layer of dense xenon. Simulations suggest this material is compressed an order of magnitude more than strong shock relations would predict. X-ray backlighting techniques have yielded images of a collapsed shock compressed to

International audience; In this paper, experimental results on radiative shocks generated by a high power laser in a xenon gas cell are presented. Two sets of experiments have been performed at the Laser pour l'Utilisation des Lasers Intenses (LULI) laboratory. Several shock parameters were simultaneously measured: shock temperature and velocities, the precursor two-dimensional (2D) time evolution, its electron density, density gradient, and temperature. Data were obtained varying initial conditions for different laser intensities and gas pressures. Comparisons with 1D and 2D radiative hydrodynamic simulations are shown for all measured parameters (shock velocity, shape, radial expansion, and temperature as well as precursor velocity and electron density).

We study analytically the Rayleigh-Taylor instability in expanding supernova gas shell. The instability appears at the inner shell surface accelerated by blowing pulsar wind. The most dangerous perturbations correspond to wavelengths comparable to the shell thickness. We analyze the fragility of the supernova remnant shell in function of the initial perturbation amplitude and the shell thickness.

In this paper a theoretical analysis of the physical processes taking place in the Electrothermal Gun (ET Gun) is presented. In a first step, using the basic conservation equations (energy, mass, charge) integrated over the whole time of the discharge, scaling laws are derived. These laws provide the temperature, the mass, the resistance of the plasma and the current going through it, as functions of the storaged electrical energy. In a second step, a 0D-time-dependent model is presented. This model takes into account the evolution of the complete system consisting in the electrical source, the plasma burner and the motion of the projectile. Special attention is given to the ablation phenomena and a microscopic description which differs from the one used previously by Loeb and Kaplan or Zoler and Cuperman is derived. Finally, comparisons with experiments are given and good agreements are obtained.

International audience; We present the set-up and the results of a supercritical radiative shock experiment performed with the LULI nanosecond laser facility. Using specific designed targets filled with xenon gaz at low pressure, the propagation of a strong shock with a radiative precursor is evidenced. The main measured quantities related to the shock (electronic density, propagation velocities, temperature, radial dimension) are presented and compared with various numerical simulations.

International audience; This paper presents some recent measurements on radiative shocks generated in a xenon gas cell using high power laser. We show new results on temperature and electronic density, and on radial expansion of the shock at various initial conditions (laser energy and gas pressure). The data obtained are compared with one-dimensional and two-dimensional hydro simulations.

The quantitative characteristics of process of excitation and development of turbulence in the mixing zone between the non-reacted hydrogen-oxygen mixture and inert gases were under the investigation. The accelerated motion is created by compression waves generated by a flame front, expanding in a combustible mixture. The experimental study includes definition of the mixing zone evolution during its motion along the channel with acceleration and subsequent deceleration.

A new mathematical approach was developed to quantify convulsant interaction between pefloxacin and theophylline in rats.Animals received each compound separately or in different combination ratios. Infusion was stopped at the onset of maximal seizures. Cerebrospinal fluid (CSF) and plasma samples were collected for HPLC drug determination. The nature and intensity of the pharmacodynamic (PD) interaction between drugs was assessed with a new modeling approach which includes (a) data transformation to create an essentially error-free X-variable and (b) estimation of an interaction parameter a by fitting a nonlinear hyperbolic model to the combination data with unweighted nonlinear regression.Drug disposition to the biophase was linear within the range of administered doses. The estimates of a suggested a Loewe antagonistic interaction between pefloxacin and theophylline at the induction of maximal seizures in rats. Similar intensity of PD interaction was observed at the dose and biophase level (alpha was -0.415 +/- 0.069 and -0.567 +/- 0.079, respectively).The suitability of the proposed model was assessed by Monte Carlo simulation. This new mathematical approach enabled the characterization of the Loewe antagonistic nature of the PD (convulsant) interaction between pefloxacin and theophylline, whereas previously used methodologies failed to do so.

The time course of arterial plasma lidocaine concentration, following an epidural anaesthesia via the sacrococcygeal or the S4-S5 trans-sacral approach, was studied in nine healthy piglets (7.8 +/- 1.3 weeks). Plasma lidocaine concentrations were measured for up to six hours after administration (5 mg/kg). Peak plasma concentration was 1.83 +/- 0.17 mg/l. Pharmacokinetic parameters determined from an independent compartment model were not different from those observed after an epidural administration of lidocaine via the sacrococcygeal space in children, except for a wide variability in the time taken to reach the maximum concentration (27.3 +/- 7.4 min) and a shorter half-life of elimination (82.8 +/- 7.0 min). The total body clearance of lidocaine was similar in piglets (17.3 +/- 1.6 ml/min/kg) to that in children. The shorter half-life of elimination was therefore attributed to a smaller volume of distribution in piglets (2.0 +/- 0.2 l/kg).

Cytochrome P450 IID6 has got typical features (genetical polymorphism, competitive inhibition, saturability) which can be at the origin of pharmacokinetic modifications of molecules using it for their metabolism. In the field of pharmacology, many molecules are substrates or inhibitors of this cytochrome. They are presented. The results of a study of the dextromethorphan variation test performed before and after 28 days of clomipramine therapy with depressed patients are explained. They show a significant decreasing of the cytochrome P450 IID6 oxidation capacities between both of these times. A patient has passed from the phenotype "effective metabolizer" to the one of "poor metabolizer" with clomipramine.