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Gel chromatography combined with specific and non-specific cyclosporin radioimmunoassays was adopted for quantitative analysis of cyclosporin and metabolites in free and protein-bound forms in blood compartments of kidney transplant patients. The analytical method was proved to be useful for the purpose, although plasma protein-bound forms of neither cyclosporin nor metabolites could be quantitated in the system. The present study also provided, by gel chromatographic analysis, additional examples to prove that concentrations of cyclosporin metabolites in blood compartments may not be deduced or inferred simply from those of cyclosporin.

The pharmacokinetic parameters of cyclosporin, a potent immunosuppressive agent, show large intra-and inter-individual variability, possibly because of the different analytical methods used. A recently developed cyclosporin-specific radioimmunoassay has been used to study the in-vivo distribution and binding characteristics of cyclosporin in whole blood, plasma and erythrocytes of fifteen renal transplant patients. The profiles of cyclosporin concentration-time curves after an oral dose of cyclosporin had either one peak (ten patients, group A) or two (five patients, group B). Essentially no difference was observed between the two groups in the relationship between equilibrium cyclosporin concentrations in erythrocyte and plasma as a function of whole-blood concentration. The equilibrium in-vivo cyclosporin concentrations in erythrocytes and plasma were, however, markedly lower than those previously observed under in-vitro conditions. The ratio of cyclosporin concentration in erythrocytes (CE) to that in plasma (CP) changed with time, in inverse proportion to the change in cyclosporin concentration in blood, over the range 0.63-2.80 in individual patients with an average of 1.36 ± 007 (mean ± s.e.m.) for group A and 1.42 ± 0.23 for group B. The apparent cyclosporin binding affinity (Kd) to erythrocytes under in-vivo conditions averaged 452.2 ± 47.6 nm (543.5 ± 57.2 ng mL−1) for group A and 419.4 ± 41.2 nm (504.1 ± 49.5 ng mL−1) for group B, whereas apparent cyclosporin binding capacity (Bmax) of the blood cell averaged 0.83 ± 0.07 nmol mL−1 for group A and 0.78 ± 0.07 nmol mL−1 for group B. Significantly reduced average Kd (262.7 ± 40.2 nm or 315.8 ± 48.9 ng mL−1, P < 001) and Bmax (0.56 ± 008 nmol mL−1, P < 005) values were observed during the period after Tmax (4–12 h after the drug ingestion) in group A patients. Apparent Kd and Bmax, determined by a nonlinear regression technique, were 131.6 ± 29.4 and 1088.0 ± 114.7 nm (158.2 ± 35.4 and 1307.8 ± 137.9 ng mL−1) and 0.178 ± 0.024 and 0.814 ± 0.078 nmol mL−1, respectively, during the 4–12 h period in group A patients. These findings reveal distinct differences in in-vivo distribution of cyclosporin and the binding characteristics of the compound to erythrocytes from those previously observed under in-vitro conditions. The significantly lower Kd of cyclosporin binding to erythrocytes during the elimination phase suggests a potential effect of cyclosporin-containing erythrocytes or of cyclosporin contained in erythrocytes during cyclosporin treatment.

We have formed a laser-induced plasma (LIP) in supercritical water (SCW) and studied associated molecular vibrations using spectroscopic methods. The accompanying forward and backward stimulated Raman scattering (SRS) of water molecules showed anisotropic behavior at supercritical conditions (>647 K and >22.1 MPa). The Raman shift of the backward SRS indicated that attractive interactions between water molecules and excess electrons generated by the LIP were dominant in the SCW. The backward SRS spectrum provided a microscopic view of the hydration environment around an excess electron, which is useful for controlling electron-driven chemical reactions and materials processing in SCW.

We generated micrometer-scale discharge in high-pressure H2O and Xe up to supercritical conditions. In our previous paper, we reported the existence of two peculiar features in the breakdown voltages under high-pressure CO2. The first one was the downward shift at the right-hand side of Paschen’s curve above about 2.5MPa, and the second one was the drastic decrease in the breakdown voltages near the critical point. We have experimentally confirmed that these features are also observed in H2O and Xe, even though there are some differences among these materials. Our theoretical fitting involving a density fluctuation term FD agrees well with the experimental results, especially for Xe. We suppose that these unique features are brought about by decreases in the electron-to-particle cross section σ, ionization potential φi, and secondary electron coefficient γ′ and changes in the discharge space.