Leflunomide is a prodrug. Its efficacy is based on conversion to an active metabolite, teriflunomide (A77 1726). The half-life of this metabolite in humans is greater than two weeks but in dogs, it approximates 24 hrs.

Therapeutic Range: In cats, Mehl et al (JVPT 2011) demonstrated ex vivo that a mean teriflunomide concentration of 16 mcg/ml inhibited 50% lymphocyte activity. Further, van Roon et al (Ann Rheu Dis 2005) demonstrated that human patients responded poorly to concentrations of the active metabolite if less than 16 mcg/ml. No studies have been done in dogs. Accordingly, a concentration greater than 16 mcg/ml is a reasonable starting for therapeutic response. Based on our assessment of responders versus no responders, all animals that responded did so at concentrations between 5 and 45 mcg/ml.

When: Drug will accumulate 50% with a 24 hr dosing interval. Monitoring can occur within 5 to 7 days of a new dosing regimen.

Sampling times: We currently recommend a single trough sample. The half-life is short enough in some animals that a peak and trough may be indicated simply to detect the short half-life in problem patients. The 24 hr half-life does suggest that the timing of sample collection be consistent if concentrations are going to be compared across time in a patient.

Other considerations: Leflunomide appears to be a substrate for both p glycoprotein and cytochrome P450. As such, drug interactions should be considered. We have measured concentrations higher than 140 mcg/ml in patients on drugs which inhibit drug metabolizing enzymes or on drugs which also are substrates for p glycoprotein.