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Primidone is a clinically useful antiepileptic drug that is metabolised to two pharmacologically active metabolites phenobarbital and phenylethylmalonamide. As data on the inter-relationship between the systemic and central nervous system pharmacokinetics of primidone and its metabolites are sparse, we have investigated their temporal inter-relationship using a freely behaving rat model which allows repeated sampling of blood (100 microl) and cerebrospinal fluid (CSF; 20 microl). After administration, by intraperitoneal injection (50, 100 or 200 mg/kg), primidone rapidly appeared in both serum (Tmax mean range 1.5-2.5 h) and CSF (Tmax mean range 2.0-3.5 h), suggesting ready penetration of the blood-brain-barrier. This was also the case for phenylethylmalonamide and phenobarbital but peak concentration occurred later. Primidone, phenylethylmalonamide and phenobarbital concentrations rose linearly and dose-dependently in both serum and CSF. The mean free fraction (free/total concentration ratio) for primidone, phenylethylmalonamide and phenobarbital was 0.86, 0.97 and 0.88, respectively, and, as their respective mean CSF/serum ratio values were 0.73, 1.06 and 0.65, it would suggest that equilibration between the blood and CSF compartments is rapid. CSF mean t(1/2) values for primidone, phenylethylmalonamide and phenobarbital were similar to those of sera and essentially paralleled the pattern seen in sera.

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A tensile/compressive-torsional biaxial testing system was employed and tensile/ compressive-torsional tests were performed for the hollow specimen, which was loaded and the austenized specimen was cooled so that pealrite transformation accompanied by transformation plasticity occurred and axial and torsional strain were measured. Furthermore, the elastic-plastic constitutive equation due to phase transformation based on the hydrostatic pressure dependent model was proposed, and the validity of this equation was discussed experimentally. The test results showed the transformation plasticity coefficient due to pearlitic transformation of S45C depends on the loading direction, and these behaviour can be appropriately expressed by the hydrostatic pressure dependent model than the isotropic model.

Description on the kinetics of austenite-pearlite and austenite-martensite transformations in connection with temperature variation and also of the elastic-plastic stresses in the course of quenching of steel was made. The volume fractions of the structures in addition to the plastic strain and the hardening parameter were regarded as internal variables, and an emphasis was placed on the metallurgical considerations on the nucleation and the growth of the phases to obtain the evolutional equations of the variables.Finite element formulations based on the weighted residual method and the principle of virtual work were presented for the analyses of the heat conduction with phase transformations and the stress and strain, respectively.As an example, the theory was applied on a solid cylinder of carbon steel cooled from above its eutectoid temperature.Several kinds of experiments were carried out on temperature change and the variation in the structural distribution was observed by microscopy and the residual stresses were measured by the Sachs' method and by X-ray diffraction technique to verify the present theory.

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