Target organ disposition and plasma pharmacokinetics of doxorubicin incorporated into albumin microspheres after intrarenal arterial administration.
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.
Kerr
D J
DJ
CRC Department of Medical Oncology, Glasgow University, United Kingdom.
Willmott
N
N
McKillop
J H
JH
Cummings
J
J
Lewi
H J
HJ
McArdle
C S
CS
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
D000418:Albumins; D004317:Doxorubicin