Cytochrome P450 (CYP) drug-drug interactions of some popular therapeutic medications administered to dogs

Summary

In-vitro canine microsome assays will be undertaken to understand the degree of hepatic metabolism of some common canine medicines: carprofen, doxycycline and pimobendan; and the influence that phenobarbitone has on their rate of hepatic metabolism.

Supervisor(s)

Associate Professor Merran Govendir

Research Location

Faculty of Veterinary Science

Program Type

PHD

Synopsis

Dogs are frequently medicated with multiple medicines, for example: some dogs may be medicated daily with an antiepileptic drug (AED) to control epileptic seizures along with a non-steroidal anti-inflammatory drug (NSAID) to control arthritic pain. Over the last 15 years it has been recognised that some drugs affect the hepatic metabolism rate of others, by either up- or down- regulating the activity of hepatic cytochrome P450 metabolism enzymes (CYPs). Information on drug interactions in companion animals lags well behind that known for people. No information exists on which CYPs metabolise some popular canine medications such as carprofen (a NSAID), doxycycline (an antibiotic), or pimobendan (increases cardiac output). This information is important because phenobarbitone (PB), the most commonly administered canine AED is a recognised inducer of many canine CYPs. If PB induces the rate of metabolism of these other medicines, they may not reach therapeutic concentrations and may require dose modification. Investigating drug interactions due to CYP modulation uses a non-patient invasive, in-vitro method using microsome assays. This project investigates the metabolic pathways of the above mentioned medicines in dogs, and whether PB increases their rate of their metabolism. Such information will be used to make recommendations on whether dose rate modifications are required in order to improve canine health outcomes.    

Additional Information

*Applicants will require some understanding on physiological pharmacokinetic processes especially metabolism and excretion.*An applicant with a BVSc Hons degree (or equivalent) is desirable *Applicants undertaking this project will develop skills in high performance liquid chromatography and microsome assay. The knowledge gained from completing this project will be helpful to establishing a research career in pharmacology and will be viewed very favourably when seeking opportunities to work with pharmaceutical companies.     *There is no scholarship attached to this project, however applicants with a good first class Honours degree or equivalent will be encouraged to apply for an Australian Postgraduate Award which is a tax-exempt stipend currently worth $23728 and CPI indexed annually http://sydney.edu.au/scholarships/research/postgraduate_awards.shtml Applications for APAs close around October 31st (for semester 1) and June 16th (for semester 2) each year.

Keywords

cytochrome, dogs, therapeutic medication on dogs, epileptic seizures on dogs

Opportunity ID

The opportunity ID for this research opportunity is: 1597

Other opportunities with Associate Professor Merran Govendir

• Investigation into the pharmacokinetics and efficacy of analgesics used in koalas