Differences between the Results Assessed by Slit Lamp Examination and Anterior Segment Photography in Terms of Cataract Grading

Purpose@#We compared the cataract grades with slit lamp examination and anterior segment photography using the Lens Opacities Classification System (LOCS) III criteria. We also explored the effect of a yellow filter on the photographic results. @*Methods@#Eighty eyes with cataracts were examined by three inspectors (1, 2, and 3). Anterior segment photographs taken by inspector 1 were divided into two groups depending on whether cortical opacity or nuclear sclerosis predominated. In each group, the cataract grades determined by inspector 1 on slit lamp examination and anterior segment photography were compared. Also, after randomly assigning the anterior segment photographs taken by inspector 1 to inspectors 2 and 3, the cataract grades of these photographs were compared to the grades of photographs taken by all inspectors using a yellow filter. @*Results@#The average cortical opacity evaluated by inspector 1 on slit lamp examination (3.48 ± 0.91) was significantly higher than that apparent on anterior segment photographs (2.35 ± 0.77) (p < 0.001). In the photographs, the average cortical opacity when a yellow filter was used was significantly higher for both inspectors 1 (p < 0.001) and 2 (p = 0.022) than when the filter was absent. The average extent of nuclear sclerosis evaluated by inspector 1 on slit lamp examination (4.08 ± 0.94) was significantly higher than that of anterior segment photography (3.73 ± 1.24) (p = 0.042). @*Conclusions@#Cataract evaluation via anterior segment photography underestimates the extent of damage compared to direct slit lamp examination. However, use of a yellow filter during photography aids cataract evaluation, especially cortical opacity.

Development of a physiologically-based pharmacokinetic model for cyclosporine in Asian children with renal impairment

This study aimed to assess the pharmacokinetics of cyclosporine A (CsA) in Asian children with renal impairment (RI) by developing a physiologically-based pharmacokinetic (PBPK) model with Simcyp Simulator. The PBPK model of Asian children with RI was developed by modifying the physiological parameters of the built-in population libraries in Simcyp Simulator. The ratio of healthy and RI populations was obtained for each parameter showing a difference between the populations. Each ratio was multiplied by the corresponding parameter in healthy Asian children. The model verification was performed with published data of Korean children with kidney disease given multiple CsA administrations. Simulations were performed with different combinations of ethnicity, age, and renal function to identify the net impact of each factor. The simulated results suggested that the effect of RI was higher in children than adults for both Caucasian and Asian. In conclusion, the constructed model adequately characterized CsA pharmacokinetics in Korean children with RI. Simulations with populations categorized by ethnicity, age, and renal function enabled to assess the net impact of each factor on specific populations.

Assessment of Hepatic Cytochrome P450 3A Activity Using Metabolic Markers in Patients with Renal Impairment

BACKGROUND: The renal function of individuals is one of the reasons for the variations in therapeutic response to various drugs. Patients with renal impairment are often exposed to drug toxicity, even with drugs that are usually eliminated by hepatic metabolism. Previous study has reported an increased plasma concentration of indoxyl sulfate and decreased plasma concentration of 4β-hydroxy (OH)-cholesterol in stable kidney transplant recipients, implicating indoxyl sulfate as a cytochrome P450 (CYP) inhibiting factor. In this study, we aimed to evaluate the impact of renal impairment severity-dependent accumulation of indoxyl sulfate on hepatic CYP3A activity using metabolic markers. METHODS: Sixty-six subjects were enrolled in this study; based on estimated glomerular filtration rate (eGFR), they were classified as having mild, moderate, or severe renal impairment. The plasma concentration of indoxyl sulfate was quantified using liquid chromatography-mass spectrometry (LC-MS). Urinary and plasma markers (6β-OH-cortisol/cortisol, 6β-OH-cortisone/cortisone, 4β-OH-cholesterol) for hepatic CYP3A activity were quantified using gas chromatography-mass spectrometry (GC-MS). The total plasma concentration of cholesterol was measured using the enzymatic colorimetric assay to calculate the 4β-OH-cholesterol/cholesterol ratio. The correlation between variables was assessed using Pearson's correlation test. RESULTS: There was a significant negative correlation between MDRD eGFR and indoxyl sulfate levels. The levels of urinary 6β-OH-cortisol/cortisol and 6β-OH-cortisone/cortisone as well as plasma 4β-OH-cholesterol and 4β-OH-cholesterol/cholesterol were not correlated with MDRD eGFR and the plasma concentration of indoxyl sulfate. CONCLUSION: Hepatic CYP3A activity may not be affected by renal impairment-induced accumulation of plasma indoxyl sulfate.