Effects of lersivirine on canine and rodent thyroid function.

Lersivirine is a nonnucleoside reverse transcriptase inhibitor (NNRTI) being developed for the treatment of HIV-1 infection. Like other NNRTIs, lersivirine is a potent enzyme inducer in rodents capable of inducing a number of hepatic enzymes including those involved in its own metabolism. Preclinically lersivirine has been associated with hepatocellular hypertrophy and thyroid gland follicular cell hypertrophy in rats, mice, and dogs. In rodents, we show that development of thyroid hypertrophy is related to the classic mechanism, namely increased thyroxine (T4) clearance secondary to induction of uridine-diphosphoglucuronosyltransferase (UDPGT) in the liver and a resulting increase in thyroid-stimulating hormone. Similarly, lersivirine-exposed dogs exhibit a significant increase in hepatic UDPGT enzyme activity along with increased T4 clearance although clear effects on serum thyroid hormone levels were less apparent. These effects on thyroid hormonal clearance in the dog suggest that thyroid gland hypertrophy in this species is due to the same mechanism shown to occur in rodents although, as expected, dogs better adapt to these effects and therefore maintain relatively normal thyroid hormonal balance. It is also notable that the minimal thyroid follicular hypertrophy that occurs in dogs does not progress as is seen in rodents. As is the case with rodents, these adaptive changes in the dog are not considered indicative of a human health risk.

Disposable plastic rodent feeders for use in an automated filling system.

Rodent feeder devices are often made of reusable, sanitizable materials such as glass and stainless steel. As part of an initiative at the authors' facility to automate the feeder filling process, disposable plastic feeding cups were proposed as a preferable alternative to standard feeders for use in a filling machine. The authors tested and validated designs for rodent meal-type feeder assemblies that incorporated plastic cups. Assemblies included stainless steel shields that prevented rats and mice from chewing on the plastic cups while allowing them full access to food. The use of disposable feeder cups that are filled and sealed automatically reduces labor associated with sanitation, enables staff to prepare feeders for several weeks in advance and limits personnel contact with feed that may contain harmful chemicals.