Pharmacokinetics and tissue distribution of SB-251353, a novel human CXC chemokine, after intravenous administration to mice

The pharmacokinetics and tissue distribution of SB-251353, a novel truncated form of the human CXC chemokine growth-related gene product beta, were studied after intravenous ad-ministration to the mouse (0.1–250 mg/kg). At the lowest dose, the clearance exceeded blood flow to the kidney. As the dose increased, clearance approached the glomerular filtration rate in the mouse. Clearance of this chemokine may be mediated by its pharmacologic receptor, CXCR2, via endocytosis with sub-sequent lysosomal degradation, as has been observed for sev-eral growth and hematopoietic factors. Apparent distribution volumes were high (1 l/kg). Moderate binding to the Duffy antigen/receptor for chemokines on erythrocytes was ob-served. Consistent with the pharmacokinetic analysis, micro-scopic autoradiography showed uptake into renal proximal tu