A Method for Measurement of Antibiotics in Human Interstitial Fluid

Abstract

To measure the antibiotic activity in interstitial fluid of volunteers, an area of skin 1 cm2 was denuded and covered with a chamber that was subsequently filled with saline. After the administration of an antibiotic, the portion that was not bound to protein was diffused out of the vascular space and equilibrated with the fluid in the chamber. At hourly intervals, the fluid was removed and immediately frozen, and the chamber was refilled. Serum was obtained simultaneously. Antibiotic activity was measured by the cup-plate and agar-well diffusion techniques. Volunteers were given each of the following antibiotics on separate days: cephalexin, ampicillin, benzylpenicillin, phenoxymethylpenicillin, nafcillin, and flucloxacillin. Antibiotics with lower percentages of protein binding diffused into the fluid of the skin window better than antibiotics with high percentages of protein binding. Flucloxacillin, 95% of which is bound to protein, had no detectable fluid levels in the skin window. The results suggest that the ability of antibiotics to diffuse into the interstitial fluid is related to the percentage of free drug in serum.