Physics guidelines for the Compact Ignition Tokamak

The goal of the Compact Ignition Tokamak (CIT)d program is to provide a cost-effective route to the production of a burning deuterium-tritium plasma, so that alpha-particle effects may be studied. A key issue to be studied in the CIT is whether alpha power behaves like other power sources in affecting tokamak plasma confinement. The program is managed by the Princeton Physics Laboratory and includes broad community involvement. Guidelines for the preliminary design effort have been provided by the Ignition Technical Oversight Committee in discussion with the tokamak community. The reference design is a tokamak with a high filed (10 T), high current (10 MA), poloidal divertor, and liquid-nitrogen-cooled coils. It is a small, high-power-density device of the type proposed by Bruno Coppi (MIT). It has a major radius of 1.23 m, a minor radius of 0.43 m, and plasma elipticity of 1.8. This paper reviews the aims of the program and the basis for the physics guidelines. The role of the CIT in the longer-term tokamak program is briefly discussed. 23 refs., 9 figs., 1 tab

Evidence of CYP3A Allosterism In Vivo: Analysis of Interaction Between Fluconazole and Midazolam

The allosteric effect of fluconazole (effector) on the formation of 1’-hydroxymidazolam (1’-OH-MDZ) and 4-hydroxymidazolam (4-OH-MDZ) from the CYP3A4/5 substrate, midazolam (MDZ), was examined in healthy volunteers. Following pre-treatment of fluconazole, AUC(4-OH)/AUC(MDZ) increased 35–62%, while AUC(1’-OH)/AUC(MDZ) decreased 5–37%; AUC(1’-OH)/AUC(4-OH) ratio decreased 46–58% by fluconazole and had no association with CYP3A5 genotype. 1’-OH-MDZ formation in vitro was more susceptible than 4-OH-MDZ formation to inhibition by fluconazole. Fluconazole decreased the intrinsic formation clearance ratio of 1’-OH-MDZ/4-OH-MDZ to an extent that was quantitatively comparable to in vivo observations. The elimination clearance of midazolam metabolites appeared unaffected by fluconazole. This study demonstrated that fluconazole alters midazolam product formation both in vivo and in vitro in a manner consistent with an allosteric interaction. The 1'-OH-MDZ/4-OH-MDZ ratio may serve as a biomarker of such interactions between midazolam, CYP3A4/5 and other putative effectors