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In recent years, several mathematical models have been developed for analysis of drug dissolution data, and many different mathematical approaches have been proposed to assess the similarity between two drug dissolution profiles. However, until now, no computer program has been reported for simplifying the calculations involved in the modeling and comparison of dissolution profiles. The purposes of this article are: (1) to describe the development of a software program, called DDSolver, for facilitating the assessment of similarity between drug dissolution data; (2) to establish a model library for fitting dissolution data using a nonlinear optimization method; and (3) to provide a brief review of available approaches for comparing drug dissolution profiles. DDSolver is a freely available program which is capable of performing most existing techniques for comparing drug release data, including exploratory data analysis, univariate ANOVA, ratio test procedures, the difference factor f (1), the similarity factor f (2), the Rescigno indices, the 90% confidence interval (CI) of difference method, the multivariate statistical distance method, the model-dependent method, the bootstrap f (2) method, and Chow and Ki's time series method. Sample runs of the program demonstrated that the results were satisfactory, and DDSolver could be served as a useful tool for dissolution data analysis.

The regulation of the phosphaturic factor fibroblast growth factor 23 (FGF23) is not well understood. It was found that administration of 1,25-dihydroxyvitamin D 3 (1,25[OH] 2 D 3 ) to mice rapidly increased serum FGF23 concentrations from a basal level of 90.6 ؎ 8.1 to 213.8 ؎ 14.6 pg/ml at 8 h (mean ؎ SEM; P < 0.01) and resulted in a four-fold increase in FGF23 transcripts in bone, the predominate site of FGF23 expression. In the Hyp-mouse homologue of X-linked hypophosphatemic rickets, administration of 1,25(OH) 2 D 3 further increased circulating FGF23 levels. In Gcm2 null mice, low 1,25(OH) 2 D 3 levels were associated with a three-fold reduction in FGF23 levels that were increased by administration of 1,25 ( FGF23 also suppresses 1␣ hydroxylase activity in the proximal renal tubule, leading to reduced circulating levels of 1,25(OH) 2 D 3 (2,10,14,15). The significance of FGF23 regulation of 1,25(OH) 2 D 3 production is not clear, but the findings that FGF23 is produced predominantly by osteoblasts in bone and that FGF23 regulates phosphate reabsorption and 1,25(OH) 2 D 3 production by the kidney raise the possibility that FGF23 may be involved in a bone-kidney axis that controls phosphate and vitamin D homeostasis (16,17). How FGF23 is integrated with the vitamin D-parathyroid hormone (PTH) axis, which plays a central role in calcium homeostasis, skeletal development, and mineralization (18), however, is not clear. Understanding the effects of 1,25(OH) 2 D 3 on FGF23 production is important, because vitamin D therapy often is used to treat FGF23-mediated hypophosphatemic disorders, such as XLH (19).In an effort to understand more fully the regulation of FGF23 expression in osteoblasts and bone, we assessed the effect of 1,25(OH) 2 D 3 administration on circulating levels of FGF23 in wild-type Gcm2 null (20) and Hyp mice (21), as well as the effects of 1,25(OH) 2 D 3 on the FGF23 transcripts in bone. In addition, we investigated the ability of 1,25(OH) 2 D 3 to regulate endogenous FGF23 transcripts and the activity of a transfected murine FGF23 promoter luciferase reporter in osteoblasts. Our findings demonstrate the importance of bone as a target for vitamin D-mediated increments in FGF23 production and suggest that FGF23 production serves as a counterregulatory hormone to enhance renal phosphate clearance in response to vitamin D-mediated increments in gastrointestinal phosphate absorption and decrements in the phosphaturic hormone PTH. Materials and Methods 1,25(OH) 2 D 3 and PTH AdministrationBoth Hyp mice (21) and C57BL/6J mice were purchased from Jackson Laboratory (Bar Harbor, ME). Male and female Gcm2 ϩ/Ϫ mice were mated to generate homozygous Gcm2 null mice that lacked parathyroid glands (22). All mice were maintained and used in accordance with recommendations in