PF-03654764 is an orally active, potent, and selective histamine H3 receptor antagonist with Ki values of 1.2 nM for human H3 and 7.9 nM for rat H3. It is often co-administered with Fexofenadine for the treatment of allergic rhinitis.

H3 receptor:7.9 nM (Ki,rat ), H3 receptor:8.98 (pKi,human), H3 receptor:1.2 nM (Ki) (human), H3 receptor:8.10 (pKi,rat)

In a whole cell assay, PF-03654764 exhibits pKi values of 8.98 and 8.10 for human H3 and rat H3, respectively. In HEK-293 cells, PF-03654764 demonstrates pKi values of 8.84 and 7.73, as well as Ki values of 1.4 nM and 19 nM for human H3 and rat H3, respectively. Notably, PF-03654764 displays >1000-fold selectivity for the H3 receptor over the other histamine receptor subtypes[1].Regarding its pharmacokinetics, PF-03654764 has a half-life (T1/2) of 120 minutes in human liver microsomes (HLM) and a clearance (CLh) of less than 5 mL/min•kg in HLM[2].

In Sprague-Dawley rats, PF-03654764 administered orally at a dose of 10 mL/kg for 14 days results in a Cmax of 8057 ng/mL and an AUC0-24 of 67400 ng•h/mL[2].
Similarly, in beagle dogs, oral administration of PF-03654764 at a dose of 1 mL/kg for 7 days yields a Cmax of 6302 ng/mL and an AUC0-24 of 18175 ng•h/mL[2].