Renal lymph concentrations of cephalosporins: The importance of protein binding and renal excretion

Summary The renal clearance, renal lymph concentrations and serum protein binding were determined in the dog for 5 cephalosporine derivatives (cephaloridine, cephalothin, cephazoline, cephacetrile, and cephradine). The protein binding for these cephalosporines was 11%, 50%, 24%, 24%, and 10% respectively. These cephalosporines were either excreted exclusively by glomerular filtration (cephaloridine and cephradine) or in addition by tubular secretion (cephalothin, cephazoline, and cephacetrile). The renal lymph concentrations of all antibiotics were significantly lower than the simultaneous arterial plasma concentrations (mean values between 64% and 84%). There was a significant negative correlation between the renal clearance and the lymph/plasma ratio of the antibiotic. There was also an indirect negative correlation between serum protein binding and the relative renal lymph concentrations. The renal clearance, therefore, but not the protein binding, has a direct effect on the lymph concentration. The renal interstitium is divided into a perivascular and a peritubular interstitium. Since lymph vessels are only present in the perivascular connective tissue, lymph concentrations can only reflect the conditions in the perivascular interstitium. Since the post-glomerular capillaries contain pores offering permeation possibilities for even high molecular substances, good tissue permeability for free as well as protein-bound antibiotics can be assumed. The interstitial concentration depends on the capillary plasma concentration and this in turn on the renal excretion mechanism of the antibiotic.