It is proposed that to achieve a therapeutic effect in schizophrenia patients, dopamine D(2)-receptor occupancy by antipsychotics within the striatum must exceed 60-65%. However, at high levels of ...D(2)-receptor occupancy, the risk of extrapyramidal symptoms (EPS) is increased. Following oral dosing of antipsychotics, peaks and troughs in plasma drug concentrations may be mirrored by fluctuations in D(2)-receptor occupancy. Paliperidone, a novel antipsychotic available as extended-release tablets (paliperidone ER), is the major active metabolite of risperidone and exhibits a plasma pharmacokinetic profile with reduced peak-trough fluctuations and consistent D(2)-receptor occupancy compared with conventional oral antipsychotic formulations. Using formulations that resemble those in clinical practice, this study provides a preclinical evaluation of the pharmacological properties of paliperidone ER and risperidone immediate-release formulation in terms of consistent antipsychotic efficacy over time and extrapyramidal symptom liability. Significant fluctuations in inhibition of d-amphetamine-induced hyperlocomotion were observed for repeated subcutaneous (SC) risperidone injections, whereas stable inhibitory efficacy was demonstrated during continuous SC paliperidone infusion. Similarly, significant fluctuations in latency on-bar were observed with repeated SC risperidone injections, whereas significantly lower latency on-bar was demonstrated following continuous SC paliperidone infusion. These results in an animal model suggest that although risperidone and paliperidone demonstrate similar pharmacologic effects, continuous administration of paliperidone achieves more stable antipsychotic efficacy with reduced motor impairment, akin to the effects observed with paliperidone ER in clinical studies.
Specific conductivities, densities, heat capacities, and enthalpies of dilution at 25‡C were measured forN,N,N-octylpentyldimethylammonium chloride (OPAC) in water-urea mixtures at various urea ...concentrations mu as functions of the surfactant concentration ms. From conductivity data, the cmc and the degree of the counterion dissociation Β of the OPAC micelles were calculated. The cmc increases linearly with increasingmu while Βvs. mu is a smooth concave curve. From the experimental thermodynamic data, the apparentYΦ and partialY2 molar properties (volumes, heat capacities, and relative enthalpies) are derived as functions of mu andms. The effect of urea on the dependences of the different properties on ms are discussed. From data in the premicellar region the standard partial molar volumesV20 and heat capacitiesCp20 were evaluated. It was observed thatV20 increases linearly withmu whileCp20 decreases. The properties of OPAC in the dispersed and micellized forms at the cmc were obtained and, therefore, the thermodynamic functions of micellization were calculated on the basis of the pseudo-phase transition model.
Conductance measurements are reported for double chain surfactants like N,N,N-octylpentyldimethylammonium (OPAC) and N,N,N-octyloctyldimethylammonium chlorides (OOAC) in water-β-cyclodextrin ...solution. From the specific conductivity data, the apparent critical micelle concentration (cmc
∗) and the degree of counterion dissociation (β) were obtained at a fixed β-CD concentration (
m
βCD
= 0.01190 mol kg
−1, besides from the cmc
∗ value and that in water (cmc) the stoichiometry of the surfactant-β-CD complex was calculated. Densities, heat capacities, enthalpies of dilution at 298 K and osmotic coefficients at 310 K were measured for the same systems; the apparent molar volumes,
V
λ
, and heat capacities,
C
λ
, of two surfactants in β-CD solution, calculated as functions of surfactant concentrations
m
s, have made possible to obtain the properties of transfer of the surfactant from water to β-CD-water solutions.
Excess enthalpies,
H
E, at 298.15 K and atmospheric pressure are reported for binary liquid mixtures of alkanenitrile + 1-chloroalkane. These experimental results, along with literature data on ...excess Gibbs energies,
G
E, are interpreted in terms of the DISQUAC group contribution model. The systems are characterized by three types of contact surfaces: nitrile (CN), chloro (Cl) and alkane. The interchange energy parameters of the alkane/CN and alkane/Cl contacts were determined independently from the study of
n-alkane + nitrile and
n-alkane + chloroalkane systems. The interaction parameters of the
CN
Cl
contacts are reported in this work. The quasi-chemical parameters are constant. The dispersive parameters depend on the environment of the CN and Cl groups. The model provides a fairly consistent description of the experimental data.
The densities, heat capacities and enthalpies of dilution at 298 K and the osmotic coefficients at 310 K were measured for
N,N,N-octyloctyldimethylammonium chloride (OOAC) in aqueous urea solution as ...a function of urea (
m
u) and surfactant (
m
s) concentrations in order to determine, in comparison with the lower homologue
N,N,N-pentyloctyldimethylammonium chloride, OPAC, the influence of the hydrophobic tail on the properties of a double-chain surfactant in the presence of an additive like urea. From specific conductivity data, the critical micelle concentration (cmc) and the degree of the counterion dissociation (β) have been calculated.
From the thermodynamic data, the molar apparent volumes,
V
φ
, heat capacities,
C
φ
, and apparent molar relative enthalpies,
L
φ
, were derived as a function of
m
u and
m
s at 298 K.
Supercritical CO2 extraction of essential oil from Thymus vulgaris leaves was studied using experimental data recently obtained in the Florys S.p.A. laboratory. Mass transfer coefficients in the ...supercritical and solid phases from extraction curves at 40°C and 20 MPa were evaluated using a mathematical model based on the local adsorption equilibrium of essential oil on lipid in leaves. The adsorption equilibrium constant was fitted to these experimental data, and internal and external mass transfer resistances were calculated, allowing identification of the mechanism controlling the extraction process.
Excess enthalpies for ternary mixtures of cyclohexane + propanone + tetrahydrofuran are studied in the framework of the DISQUAC group contribution model. The study is extended to the binary mixtures ...involved. The DISQUAC analysis is developed using interchange coefficients determined by the binary mixtures; a good representation of experimental data has been obtained even if no ternary interactions are taken into account.
Excess molar enthalpies of the ternary mixture: tetrahydrofuran + cyclohexane + butanenitrile and of the binary mixtures involved have been measured at 298.15 K by means of a flow microcalorimeter.
...The DISQUAC analysis is developed using interchange coefficients previously determined for the binary mixtures. Even neglecting ternary interactions, it is possible to obtain a satisfactory representation of the ternary system.
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