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Intraprostatic Chemotherapy: Distribution and Transport Mechanisms

Authors' Affiliations: ¹ College of Pharmacy and ² James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio

Requests for reprints: M. Guillaume Wientjes, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210. Phone: 614-292-6488; Fax: 614-688-3223; E-mail: wientjes.1{at}osu.edu.

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, 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.

Key Words: prostate cancer • doxorubicin • tissue pharmacokinetics • regional chemotherapy