Diffusion of Drugs into Prostatic Fluid and Milk

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Abstract
THE PROSTATIC FLUID/PLASMA CONCENTRATION RATIO of various sulfonamides, antibiotics and antibacterial agents, and the milk/plasma ratio of sulfonamides and basic drugs have been quantitatively correlated with the degree of dissociation, as represented by log U/D, and the partition coefficient (log P). Because of the lower pH values of the prostatic fluid (6.6) and milk (6.8) as compared with the plasma pH (7.4), the degree of dissociation appears to be the most important factor in determining the distribution of these weak acids or bases. Partition coefficient also plays a secondary role. The log Po for maximum diffusion into milk is lower than that for maximum gastrointestinal, buccal or percutaneous absorption. This may be attributed to plasma protein binding which prevents diffusion of the drug from the blood circulation into the milk since high lipophilicity favors protein binding. The clinical implications of the correlations obtained are discussed.