Tissue Distribution of Penicillins.

WHILE it is of obvious importance to determine the antibacterial activity of a penicillin in the blood it is perhaps of greater importance to know what concentrations are present in the extravascular fluids. In view of the current interest in protein binding and its influence on activity it is also of importance to determine in what way binding influences distribution throughout the body. Usually methods for estimating tissue levels of antibiotics have consisted mainly of grinding the tissue or organ in a homogeniser with the appropriate buffer, spinning down the debris and estimating the penicillins in the supernatant. The total amount of penicillin present is calculated and then expressed as the amount per gram of tissue, wet or dry weight. However these figures give very little information about the actual tissue levels. Depending on the vascularity of the organs they may reflect largely the blood levels. Alternatively, they may give quite erroneous results due to specific concentration within the organ, for example, the high levels found in the liver and kidney merely reflect the high concentration in the bile and urine. It is highly improbable that there is specifically high concentration of the antibiotics in the intracellular space of the liver and kidney. Hence it is very difficult to get a true figure for the amount of penicillin in tissues. We therefore estimated the concentration of penicillin in inflammatory fluids and lymph which can be obtained in adequate quantities for assay purposes. In addition we determined the penicillin concentration in granuloma tissue. For the studies, four penicillins were selected-phenethicillin, phenoxymethylpenicillin, cloxacillin and ampicillin. In order that all the results should pertain to the one species the serum protein binding was determined for each using rat serum by the ultrafiltration technique. The assay procedure was the cup plate technique using Sarcina lutea as the test organism, the usual precautions necessary for assaying in the presence of protein being observed. (Table I).