Maraviroc

Maraviroc (UK-427857) is a selective CCR5 antagonist with activity against human HIV. IC50 & Target:IC50: 3.3 nM (MIP-1α), 7.2 nM (MIP-1β), 5.2 nM (RANTES)^[1] In Vitro: Maraviroc (UK-427857) is a selective CCR5 antagonist with potent anti-human immunodeficiency virus type 1 (HIV-1) activity. Maraviroc inhibits the downstream event of chemokine-induced intracellular calcium redistribution, with IC₅₀s ranging from 7 to 30 nM obtained against MIP-1β, MIP-1α and RANTES.
Maraviroc (UK-427857) is active (IC₉₀) at low nanomolar concentrations against HIV-1 Ba-L (a lab-adapted R5 strain) when measured in a 5-day antiviral assay using either isolated multiple (pooled) donor PBMC (IC₉₀, 3.1 nM), single-donor PBMC (IC₉₀, 1.8 nM) or PM-1 cells (IC₉₀, 1.1 nM)^[1]. In Vivo: Clearance values are moderate to high in both rat and dog species following i.v. administration (74 and 21 mL/min/kg, respectively). Maraviroc also has a moderate volume of distribution in both species (4.3 to 6.5 liters/kg). The half-life values of maraviroc are 0.9 h in the rat and 2.3 h in the dog. Following oral administration (2 mg/kg) to the dog, the C_max(256 ng/mL) occurs 1.5 h. post-dose, and the bioavailability is 40%. For the rat, investigation of the concentrations obtain in the portal vein following oral administration indicated that approximately 30% of the administered dose is absorbed from the intestinal tract^[1]. In the DSS/TNBS colitis and in the transfer model, Maraviroc attenuates development of intestinal inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes^[2]