Sustained CCR1 blockade correlates with an effective anti-inflammatory response in a rodent thioglycollate-induced peritonitis assay and coverage levels achieved in the mouse myeloma assay. (A) CCX721 was administered in oral dosages of 3, 30, or 300 mg/kg twice daily in a rat thioglycollate-induced peritonitis assay, using cell count in the peritoneal lavage as the primary readout. (B) Functional inhibition of rat CCR1 by CCX721 over a 24-hour period, calculated from the PK measurements taken in satellite animals and in vitro CCX721 dose-response inhibition of CCR1-mediated leukocytes in 100% rat serum. (C) Chemotaxis of mouse thioglycollate-elicited leukocytes toward mouse CCL3 in 100% mouse serum and in the presence of various concentrations of CCX721 (n = 8 replicates per point, assay repeated 3 times). (D) Functional inhibition of mouse CCR1 by a 100-mg/kg orally administered dose of CCX721 given twice daily over a 24-hour period, calculated from the PK measurements taken in satellite animals and in vitro CCX721 dose-response inhibition of CCR1-mediated leukocytes in 100% mouse serum. ***P < .001 (Student t test).