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Methotrexate Levels in the Interstitial Space and Seminiferous Tubule of Rat Testis

Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland 20205 [R. R., D. G. P.]; Kyle Metabolic Unit, Walter Reed Army Medical Center, Washington, D. C. 20012 [R. A. V., S. B.]; and Childrens Orthopedic Hospital Medical Center, Seattle, Washington 98105 [W. A. B.]

The ability of methotrexate (MTX) to pass from the blood into the interstitial space and seminiferous tubule of the rat was investigated using testicular micropuncture. MTX was administered to anesthetized adult Wister rats via a femoral vein cannula. Constant plasma levels of MTX were achieved by giving a priming dose followed by a constant infusion of 1, 10, or 100 mg/kg/hr with 6 to 27 rats studied at each dose. Blood (via a jugular vein cannula), testicular interstitial fluid, and seminiferous tubule fluid (via direct micropuncture) were periodically sampled during the 4 hr of drug infusion.

Under steady-state conditions, when compared to corresponding plasma values, MTX levels were 2- to 4-fold lower in the testicular interstitial fluid and 18- to 50-fold lower in the seminiferous tubule. These results indicate that, in the rat, a significant blood-testis barrier to MTX exists at the tubular but probably not at the capillary-interstitial level. If these results can be extrapolated to humans, they do not provide a pharmacological explanation for the frequent occurrence of leukemic relapse in the interstitium of the testes in boys with acute lymphocytic leukemia.

¹ Present address: Catholic University of Rome, Department of Pediatrics, Largo A. Gemelli 8, Rome, Italy.

² To whom requests for reprints should be addressed, at Pediatric Oncology Branch, National Cancer Institute, Building 10, Room 3B03, Bethesda, Md. 20205.

Received 8/10/81. Accepted 1/20/82.

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