Precautions in drug administration in cats - Drug sensitiveness in Cats

Drug sensitiveness in Cats

Drug therapy in feline patients has many potential roadblocks: differences in drug metabolism between cats and other species, which make dose extrapolations difficult: a paucity of good safety and dose optimization studies in cats: the relative lack of approved drugs with associated efficacy data in cats compared with dogs: the need for reformulation of many drugs designed for larger patients: and the difficulty in administering medications to many cats. 

Differences in Drug Metabolism in Cats 

Cats have important differences in drug metabolism compared with humans and dogs, two species from which feline dosages are often extrapolated. It is well known that cats are deficient in glucuronidation of some xenobiotics: for example, UDP-glucuronosyltranferase (UGT) activity for acetaminophen is tenfold lower in cats compared with dogs and humans. This is due to a nonfunctional feline pseudogene for UGT1A6, the UGT isoform that metabolizes acetaminophen in humans. This same enzyme glucuronidates morphine and serotonin and contributes to the metabolism of silybin (in milk thistle). Glucuronidation is therefore deficient for many drugs in cats . However, cats are able to normally glucuronidate endogenous compounds such as thyroxine and bilirubin.

Cats are also deficient in the enzyme thiopurine methyltransferase, which metabolizes thiopurine drugs such as azathioprine. The activity of this enzyme, which can be measured in red blood cells, is 80% to 85% lower in cats than in dogs. This may explain why cats treated with azathioprine are especially sensitive to myelosuppression, which is a dose-dependent side effect of this drug. Further individual variability in thiopurine methyltransferase among cats (almost tenfold) can be attributed to genetic polymorphisms in the feline gene, such that there is overlap between some “high-activity" cats and some “low-activity” dogs. However, a relationship between polymorphisms in thiopurine methyltransferase and azathioprine response has not yet been established in either cats or dogs.