Intraprostatic chemotherapy: distribution and transport mechanisms.
OBJECTIVE
The present study evaluated the tissue distribution and targeting advantage of intraprostatic chemotherapy.


METHODS
We studied the delivery and spatial distribution of a fluorescent drug, doxorubicin, in the prostate of beagle dogs, after intraprostatic or i.v. administration. Drug concentrations were measured using high-performance liquid chromatography and confocal fluorescence microscopy.


RESULTS
I.v. and intraprostatic injections yielded qualitatively and quantitatively different doxorubicin distribution in the prostate. A relatively homogeneous distribution was found after i.v. administration, whereas intraprostatic injection yielded a highly heterogeneous distribution with >10-fold higher concentrations localized in a cone-shaped glandular lobule bound by fibromuscular stroma, compared with other parts of the prostate. Compared with i.v. injection, intraprostatic injection yielded, on average, approximately 100-fold higher tissue-to-plasma concentration ratio, ranging from 963-fold near the injection site to 19-fold in the contralateral half of the prostate. The drug distribution within the prostate further suggests an important role for acinar flow in intraprostatic drug transport.


CONCLUSIONS
Intraprostatic administration represents a viable option to deliver high drug concentrations within the prostate. The results further suggest the fibromuscular stroma separating the prostatic lobules as a major barrier to drug transport and convective flow as an important drug transport mechanism in the prostate.
Wientjes
M Guillaume
MG
College of Pharmacy and James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA. wientjes.1@osu.edu
Zheng
Jenny H
JH
Hu
Leijun
L
Gan
Yuebo
Y
Au
Jessie L-S
JL
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001692:Biological Transport; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin