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Clin Cancer Res. 2005 Jun 1;11(11):4204-11.

Intraprostatic chemotherapy: distribution and transport mechanisms.

Author information

1
College of Pharmacy and James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA. wientjes.1@osu.edu

Abstract

PURPOSE:

The present study evaluated the tissue distribution and targeting advantage of intraprostatic chemotherapy.

EXPERIMENTAL DESIGN:

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.

PMID:
15930358
DOI:
10.1158/1078-0432.CCR-04-1969
[Indexed for MEDLINE]
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