Vol. 118, October Printed in U.SA.

THE JOURNAL OF UROLOGY

Copyright © 1977 by The Williams & Wilkins Co.

MINOCYCLINE DIFFUSION INTO BENIGN PROSTATIC HYPERPLASIA TERRY W. HENSLE, GEORGE R. PROUT, JR. and PAMELA GRIFFIN From the Urological Service, Massachusetts General Hospital and the Department of Surgery, Harvard Medical School, Boston, Massachusetts

ABSTRACT

lipid soluble tetracycline that has generated interest in the treatment of chronic was evaluated for its possible ability to be concentrated in benign prostatic hyperplasia. Drug levels in the prostate, plasma, fat, muscle and urine were measured in patients undergoing prostatectomy after preoperative intravenous minocycline. The concentrations of the drug in prostate and serum were dose (4.16 versus 3.01 µg. per gm.), while drug levels in striated muscle and fat were consistently lower (2.92 and 0.77 µ.,g. per gm.). Higher preoperative doses of the drug yielded higher tissue levels. Drug delivery closer temporally to the operation serum and prostatic levels as opposed to striated muscle and fat, suggesting a diffusion of the drug into benign prostatic hyperplasia. is a semisynthetic tetracycline that recently has generated interest in dealing with chronic prostatitis. 1." The drug has a broad antibacterial spectrum with a high degree of activity against the bacterial cell wall.1. 3 Minocycline, like all tetracyclines, is 70 to 80 per cent protein-bound in ~-·------· but it is the most lipid soluble T.TT!'lf'v,c, available. The drug is dissociated as an other tetracyclines but it does have dissociation constants of 7. 8 and 9 .3. 4 These characteristics enable minocycline to diffuse readily across the epithelium of the prostatic acinus. The characterization of physical properties necessary for antibiotic diffusion into the prostate has been defined and an animal model demonstrating minocycline con-

p.m. on the evening before the operation, followed by another dose of 100 mg. intravenously on call to the operating room at 10 a.m. on the day of the operation, for a total dose of 300 mg. preoperatively. Eight of the 20 patients studied received more than the protocol dosage of minocycline, receiving 300 mg. at night and 200 mg. immediately preoperatively (fig. 1 and table 1). Tissue for study taken at the operation included prostatic adenoma, fat and striated muscle, as well as serum and urine. The excised prostatic tissue was washed repeatedly with saline TABLE

1. Concentrations of minocycline in benign prostatic

hyperplasia and other tissues Pt. No.

10

6.95

0.74

FIG. 1. Concentrations of minocycline in benign prostatic hyperplasia and oth2r tissues.

centration in the canine prostate has been developed." These experimental data along with recent clinical evidence of minocycline's effectiveness in the control and treatment of chronic prostatitis in the human 2 ' 7 prompted us to design a study that would yield data concerning the concentration of minocycline in benign nr,,Q,,,,,,.. hyperplasia. MATERIALS AND METHODS

Twenty pw""'·""" undergoing open prostatectomy for benign hyperplasia were studied prospectively. In this study group 200 mg. minocycline were given intravenously at 10 Accepted for publication December 10, 1976. Supported in part by a grant from Lederle Laboratories. 609

168--80 113-85 191-08 000-72 040-87* 003-94* 052-73* 194-79 007-72*· t 052-42*· t 026-82*· t 150-90 034-29 147-85* 178-68* 166-69 181-85 099-90 179-52 198-65 Mean Standard deviation Standard error

Prostate Muscle Fat (µ,g./gm.) (µ,g./gm.) (µ.g./gm.) 2.84 2.99 1. 74 2.82 3.62 3.61 5.78 3.27 11. 70 7.23 7.14 3.95 4.85 2.14 4.57 3.39 2.63 3.03 3.00 2.83 4.16 ±2.32 ±0.52

3.57 0.76 0.83 0.29