Predicting in vivo absorption of chloramphenicol in frogs using in vitro percutaneous absorption data.

Background: Infectious disease, particularly the fungal disease chytridiomycosis (caused by Batrachochytrium dendrobatidis), is a primary cause of amphibian declines and extinctions worldwide. The transdermal route, although offering a simple option for drug administration in frogs, is complicated by the lack of knowledge regarding percutaneous absorption kinetics. This study builds on our previous studies in frogs, to formulate and predict the percutaneous absorption of a drug for the treatment of infectious disease in frogs.

Can models of percutaneous absorption based on in vitro data in frogs predict in vivo absorption?

The primary aim of in vitro testing of chemicals delivered via the percutaneous route is to predict the absorption that would ensue if exposure occurred in live animals. While there is mounting evidence that in vitro diffusion studies in mammalian skin can provide valid information regarding likely in vivo absorption, little is known whether such a correlation exists between in vitro diffusion testing and in vivo blood levels in amphibians. The current study used previously-reported in vitro absorption data for caffeine, benzoic acid, and ibuprofen across isolated skin from the cane toad (Rhinella marina) to produce a series of linear mixed-effect models of the absorption parameters flux and permeability coefficient (Kp).

Percutaneous absorption between frog species: Variability in skin may influence delivery of therapeutics.

Frogs have permeable skin, so transdermal delivery provides a practical alternative to traditional dosing routes. However, little is known about how frog skin permeability differs interspecifically, and there are different reported clinical outcomes following topical application of the same chemical in different frog species. This study collated in vitro absorption kinetic data previously reported for two frog species: the green tree frog (Litoria caerulea) and the cane toad (Rhinella marina), and used linear mixed-effects modelling to produce a model of absorption.

Permeability of frog skin to chemicals: effect of penetration enhancers.

Rarely do commercial chemical products contain solely the active chemical/ingredient. It is therefore important to consider whether ingredients other than the active may: 1) alter absorption of the active chemical, or 2) be absorbed themselves, resulting in systemic effects. Frogs have highly permeable skin and are routinely exposed to commercial chemical products in the environment or therapeutically.

Effects of skin region and relative lipophilicity on percutaneous absorption in the toad Rhinella marina.

Owing to the dynamic interaction between frog skin and the environment, xenobiotics in frog habitats are of particular concern, and knowledge of percutaneous absorption in frog skin is necessary for risk-mitigation purposes. Baseline transdermal kinetics in adult aquatic and arboreal frog species have recently been reported; however, there is little information regarding absorption kinetics in adult terrestrial species. The present study investigated the in vitro absorption kinetics of 3 model chemicals-caffeine, benzoic acid, and ibuprofen-through different skin regions in the terrestrial toad Rhinella marina.

Regional variation in percutaneous absorption in the tree frog Litoria caerulea.

Frog skin structure and physiology differs between skin regions, however little is known about how these differences affect transdermal absorption of chemicals. Further, no information is available regarding how the relative lipophilicity of a chemical influences its transdermal pharmacokinetics in frog skin. This study investigated the in vitro percutaneous absorption of three model chemicals - benzoic acid, caffeine, and ibuprofen - through dorsal and ventral skin of the tree frog Litoria caerulea.

Stability of sodium valproate tablets repackaged into dose administration aids.

Objectives: Since sodium valproate, a commonly used antiepileptic drug, has been reported to be unstable in the presence of moisture, our objective was to investigate the effect of repackaging into dose administration aids.

Methods: Sodium valproate 100 mg immediate-release tablets were repackaged and stored for 56 days at accelerated conditions (40 degrees C/75% relative humidity), room temperature (25 degrees C) and under refrigeration (2-8 degrees C). Samples were analysed at 3, 7, 10, 14, 21, 35, 49 and 56 days to determine chemical stability using high-performance liquid chromatography, while physical testing included assessment of weight changes and dissolution behaviour.