Published by Elsevier Ireland Ltd.”
“Objectives: The aim of the study was to predict human intestinal permeability and the fraction absorbed of an oral dose of a promising trioxane anti-malarial drug (CDRI 99/411) using
the single-pass intestinal perfusion technique (SPIP) in rats.
Methods: Effective permeability coefficients (P(eff)) in anaesthetized rats were determined for marker compounds and the trioxane derivative 99/411. Drug solution in perfusion buffer was perfused through intestine with a flow rate of 0.2 ml/min and samples were taken from an outlet tubing at different time points up to 120 min. Drug concentrations in samples were determined using RPHPLC.
Key findings: The effective permeability coefficient values of marker VX-680 mw compounds obtained in rats were compared with published data for human intestinal permeability (P(eff) ((human))) and human fraction absorbed (Fa ((human))) to establish an in-house model. Strong correlations were found between rat and human values for markers buy LCL161 (P(eff (human)) = 1.039 P(eff) ((rat)) – 0.1815; R(2)=0.970 and Fa (human) = 0.1562In (P(eff (rat))) + 0.7232; R(2) = 0.927). Subsequently the human
permeability and fraction dose absorbed in human were predicted for 99/411 using the obtained rat permeability value and established correlations. P(eff) in human predicted from the model was found to be 7.05 x 10(-4) cm/s and F(a) value in human was predicted around 1.
Conclusions: Considering the high correlation of
rat P(eff) values with those of human reported values, it can be concluded that the developed in-house model is reliable and can be used preliminarily, to predict human permeability and fraction dose absorbed of any test compound. JIB-04 nmr From predicted results, 99/411 was found to have high permeability and possibly complete absorption in human.”
“Objective: A close relationship between reactive oxygen species (ROS) and myringosclerosis, which is a common complication of myringotomy, was recently reported. The objective of this study was to measure ROS levels directly in rat tympanic membranes using luminol-aided chemiluminescence (CL) in order to compare the levels of ROS after incisional and radiofrequency (RF) myringotomy.
Methods: Fifteen Sprague-Dawley rats were separated into three groups of five animals each. Bilateral myringotomies were made using an appropriate myringotomy lancet in Group 1 and RF in Group 2. Group 3 served as the control group with no myringotomy. Twenty-four hours after the procedure, all tympanic membranes were inspected with an otomicroscope and then excised for the measurement of ROS using luminol-aided CL.
Results: The mean ROS level in Group I was significantly higher than that in Groups 2 and 3 (p < 0.05 for both). The difference in mean ROS level between Groups 2 and 3 was not significant (p > 0.05).