Investigating Soil-Root Interactions with the Numerical Model R-SWMS.

In this chapter, we present the Root and Soil Water Movement and Solute transport model R-SWMS, which can be used to simulate flow and transport in the soil-plant system. The equations describing water flow in soil-root systems are presented and numerical solutions are provided. An application of R-SWMS is then briefly discussed, in which we combine in vivo and in silico experiments in order to decrypt water flow in the soil-root domain. More precisely, light transmission imaging experiments were conducted to generate data that can serve as input for the R-SWMS model. These data include the root system architecture, the soil hydraulic properties and the environmental conditions (initial soil water content and boundary conditions, BC). Root hydraulic properties were not acquired experimentally, but set to theoretical values found in the literature. In order to validate the results obtained by the model, the simulated and experimental water content distributions were compared. The model was then used to estimate variables that were not experimentally accessible, such as the actual root water uptake distribution and xylem water potential.

Clinical pharmacology of alcaftadine, a novel antihistamine for the prevention of allergic conjunctivitis.

PURPOSE: In this report, we characterize the in vitro pharmacokinetic properties of a new antihistamine, alcaftadine. In addition, we report results from phase 1 studies of several ophthalmic formulations of alcaftadine and examine the pharmacokinetic properties of one formulation in detail. METHODS: In vitro pharmacology employed a human liver microsome assay combined with index substrates or inhibitors for specific cytochromes. Metabolic fate of (14)C-alcaftadine was determined by high-performance liquid chromatography-based separation of parent compound from metabolites. Plasma protein binding was determined by equilibrium dialysis using (3)H-labeled alcaftadine and (3)H-labeled alcaftadine carboxylic acid metabolite. Relative tolerability (comfort) of 4 concentrations and 3 formulations of alcaftadine ophthalmic solution was assessed in 2 double-masked, randomized, placebo-controlled, contralateral studies in which formulations were compared to Tears Naturale II (placebo) in normal adult subjects. Data analysis focused on the mean differences in subject-reported drop comfort scores (within each dose level, at each time point) and compared the study-treatment eye with the placebo eye. Pharmacokinetics of alcaftadine 0.25% ophthalmic solution were determined in an open-label, single-center study after a single bilateral dose and after 7 days of once-a-day bilateral doses in healthy subjects 18-55 years old. RESULTS: Alcaftadine is not significantly metabolized by microsomal cytochromes, but it is rapidly converted to the carboxylic acid metabolite by one or more cytosolic enzymes. Neither the parent compound nor its carboxylic acid metabolite displayed significant plasma protein binding. Over a range of formulations and concentrations (0.05%-0.5%), alcaftadine was well tolerated and subjects reported little or no discomfort or taste perversion in any treatment group. Pharmacokinetic studies showed that both the parent compound and the carboxylic acid metabolite reach peak serum levels within minutes of administration and fall below detectable levels within 3 h of dosing. CONCLUSIONS: Based upon pharmacokinetic and phase 1 studies, the novel antihistamine alcaftadine is an appropriate drug for use as an ophthalmic formulation for prevention and treatment of ocular allergic conditions such as allergic conjunctivitis (alcaftadine ophthalmic solution 0.25% was recently approved for use by the FDA). Topical administration of alcaftadine 0.25% ophthalmic solution was well tolerated and had an acceptable safety profile.