Safety data on 19 vehicles for use in 1 month oral rodent pre-clinical studies: administration of hydroxypropyl-ß-cyclodextrin causes renal toxicity.

Potential new drugs are assessed in pre-clinical in vivo studies to determine their safety profiles. The drugs are formulated in vehicles suitable for the route of administration and the physicochemical properties of the drug, aiming to achieve optimal exposure in the test species. The availability of safety data on vehicles is often limited (incomplete data, access restricted/private databases). Nineteen potentially useful vehicles that contained new and/or increased concentrations of excipients and for which little safety data have been published were tested. Vehicles were dosed orally once daily to HanWistar rats for a minimum of 28days and a wide range of toxicological parameters were assessed. Only 30% (w/v) hydroxypropyl-ss-cyclodextrin was found unsuitable owing to effects on liver enzymes (AST, ALT and GLDH), urinary volume and the kidneys (tubular vacuolation and tubular pigment). 20% (v/v) oleic acid caused increased salivation and hence this vehicle should be used with caution. As 40% (v/v) tetraethylene glycol affected urinary parameters, its use should be carefully considered, particularly for compounds suspected to impact the renal system and studies longer than 1month. There were no toxicologically significant findings with 10% (v/v) dimethyl sulphoxide, 20% (v/v) propylene glycol, 33% (v/v) Miglyol (R) 812, 20% (w/v) Kolliphor (R) RH40, 10% (w/v) Poloxamer 407, 5% (w/v) polyvinylpyrrolidone K30 or 10% (v/v) Labrafil (R) M1944. All other vehicles tested caused isolated or low magnitude effects which would not prevent their use. The aim of sharing these data, including adverse findings, is to provide meaningful information for vehicle selection, thereby avoiding repetition of animal experimentation. Copyright (c) 2015 John Wiley & Sons, Ltd. For pre-clinical testing, drugs are formulated in vehicles that achieve the best possible exposure. Availability of safety data on vehicles is often limited. Nineteen potentially useful vehicles, for which little safety data have been published, were tested in the rat (28 days). 30% (w/v) hydroxypropyl-ss-cyclodextrin was found unsuitable owing to effects on liver enzymes, urinary volume and the kidneys. Use of 20% (v/v) oleic acid (increased salivation) and 40% (v/v) tetraethylene glycol (changes in urinary parameters) should be carefully considered.