title: Target organ disposition and plasma pharmacokinetics of doxorubicin incorporated into albumin microspheres after intrarenal arterial administration.
abstract: We synthesized doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH)-loaded human albumin microspheres (containing approximately 1% doxorubicin w/w) between 15 and 20 micron in diameter. Intrarenal arterial administration of 99mTC-labeled microspheres demonstrated a high renal entrapment ratio (97% of recovered radioactivity). The pharmacokinetics and metabolism of doxorubicin are different when it is administered in microspherical form. Peak plasma levels are lower (16 ng/ml versus 135 ng/ml) compared with treatment by a doxorubicin solution. Histologic studies showed that the microspheres were trapped within capillaries and small arterioles in the renal vascular arcade. It is apparent that chemoembolization with doxorubicin-loaded microspheres significantly reduces systemic exposure to the antineoplastic agent, and maintains intrarenal drug levels.
authors.affiliation: CRC Department of Medical Oncology, Glasgow University, United Kingdom.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kerr
authors.forename: N
authors.initials: N
authors.lastname: Willmott
authors.forename: J H
authors.initials: JH
authors.lastname: McKillop
authors.forename: J
authors.initials: J
authors.lastname: Cummings
authors.forename: H J
authors.initials: HJ
authors.lastname: Lewi
authors.forename: C S
authors.initials: CS
authors.lastname: McArdle
mesh_terms: D000418:Albumins; D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007269:Injections, Intra-Arterial; D007668:Kidney / Q000098:blood supply; D007678:Kidney Glomerulus / Q000098:blood supply; D008657:Metabolic Clearance Rate; D008863:Microspheres; D011817:Rabbits; D014018:Tissue Distribution
chemical_list: D000418:Albumins; D004317:Doxorubicin