Itraconazole is a triazole antifungal agent with a broad spectrum of activity. It is well tolerated and highly ef®cacious, particularly because its main metabolite, hydroxy-itraconazole, also has considerable antifungal activity. Two new formulations of itraconazole, an oral solution and an intravenous formulation, have recently been developed, which combine lipophilic itraconazole with cyclodextrin. These formulations have improved the solubility of itraconazole, leading to enhanced absorption and bioavailability compared with the original capsule formulation, without having an impact on the tolerability pro®le of itraconazole. The oral solution and intravenous formulations of itraconazole produce consistent plasma concentrations and are ideal for the treatment of systemic fungal infections in a wide range of patient populations. The additional¯exibility offered by the different routes of administration means that itraconazole treatment can be speci®cally tailored for use in all patients, including children and those requiring intensive care.

The pharmacokinetics and safety of an intravenous hydroxypropyl-␤-cyclodextrin solution of itraconazole administered for 7 days followed by itraconazole oral solution administered at 200 mg once or twice daily for 14 days were assessed in 17 patients with hematologic malignancies. Steady-state plasma itraconazole concentrations were reached by 48 h after the start of intravenous treatment. The mean trough plasma itraconazole concentration at the end of the intravenous treatment was 0.54 ؎ 0.20 g/ml. This concentration was not maintained during once-daily oral treatment but increased further in the twice-daily treatment group, with a trough itraconazole concentration of 1.12 ؎ 0.73 g/ml at the end of oral treatment. As expected in the patient population studied, all patients experienced some adverse events (mainly gastrointestinal). Biochemical and hematologic abnormalities were frequent, but no consistent changes occurred. In conclusion, 7 days of intravenous treatment followed by 14 days of twice-daily oral treatment with itraconazole solution enables plasma itraconazole concentrations of at least 0.5 g/ml to be reached rapidly and to be maintained. The regimen is well tolerated and has a good safety profile.

The preparation of charge-stabilized suspensions of small phosphor particles (0.14.3 pm) and their coupling with antibodies to immunoreactive conjugates is described. Phosphor particles consisting of yttriumoxisulfide activated with europium served as a model system in the evaluation of the stabilizing properties of several polycarboxylic acids. The optimal reagents were then applied to other phosphors which differ in spectral characteristics as well as in luminescence lifetime. These phosphors were ground to a size of 0.1-0.3 pm and proteins or other macromolecules were adsorbed to the phosphor particles to prepare conjugates of different physico-chemical properties. A time-resolved microscope, suitable for real time visualization of the time-delayed luminescence of the immunophosphors by the human eye, is described in detail. Since most phosphors require excitation with far UV light, a special fluorescence microscope allowing far UV excitation was developed for conventional visualization of the luminescence emitted by the phosphor. The possibility of multiple color labeling using various phosphor conjugates was demonstrated in a model system consisting of haptenized latex beads. o 1992 Wiley-Liss, Inc.Key terms: Delayed fluorescence, phosphorescence, immunophosphors, timeresolved microscopy, multiparameter immunocytochemical staining, far UV excitation fluorescence microscopy INTRODUCTION Fluorescent immunocytochemical assays are increasingly utilized for a variety of applications in pathology, oncology, and genetics, mainly because fluorescent labels are very well suited for simultaneous detection of multiple antigens (1,9,15). A disadvantage of these methods, however, is the fact that their theoretical sensitivity is hardly reached because of confounding nonspecific fluorescence due to autof luorescence, fixative induced fluorescence of cells and tissues, and autofluorescence of the optical components of the microscopic system. The contrast between specific fluorescence and autofluorescence can be enhanced by using dyes which are excited a t longer wavelengths and emit in the redhear-infra-red part of the spectrum (16), or better by applying time-resolved microscopy.Autofluorescence generally is a rapidly decaying process with fluorescence lifetimes in the range of 1-100 ns, whereas phosphorescence and delayed luminescence have lifetimes in the range of hundreds of micro-

This study demonstrates the nasal tolerance, safety and efficacy of Nazolam. When considering the preparation time needed for obtaining venous access, conscious sedation can be achieved in the same time span as needed for intravenous midazolam. Nazolam may offer important advantages in conscious sedation.

The results show that current-dependent delivery of apomorphine is possible in vivo at acceptable levels of skin irritation. Excellent correlation was found between the calculated in vivo transport rates and the rates that were previously obtained in vitro.