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Perit Dial Int 6(3): 144-147 1986
© 1986 International Society for Peritoneal Dialysis
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REVIEWS AND ORIGINAL ARTICLES

DRUG-PROTEIN BINDING DURING CONTINUOUS AMBULATORY PERITONEAL DIAL YSIS

Gene D. Morse, Carolyn Rowinski, Patricia E. Lieveld and J. Joseph Walshe

From the Departments of Medicine and Pharmacy, State University of New York at Buffalo, Erie County Medical Center, Buffalo, New York, 14215.

This study of drug-protein binding in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) measured the serum and dialysate binding of cefamandole -an acidic, cephalosporin antibiotic. Ten CAPD patients, five with and five without peritonitis received a 1.0 g intraperitoneal dose of cefamandole; serum and dialysate was sampled at 4, 10, and 24 h after drug administration. Binding also was studied in serum obtained from five chronic hemodialysis patients and five normal volunteers. Equilibrium dialysis was used to determine protein binding and high performance liquid chromatography to measure cefamandole. Mean fraction unbound (fu) serum values for CAPD patients were 0.35 ± 0.04 (noninfected) and 0.37 ± 0.14 (peritonitis). In comparison, the fu values in hemodialysis patients were 0.41 ± 0.19 and 0.15 ± 0.02 in normal volunteers. Greater than 90% of cefamandole in dialysate was unbound suggesting that antibiotics, which cross the peritoneal membrane, are present in the free, microbiologically active form.

In the presence of impaired renal function alterations in drug-protein binding often are attributed to the accumulation of endogenous compounds that compete with acidic drugs for binding sites on serum albumin (1). In addition, it has been suggested that structural aberrations in the albumin molecule and hypoalbuminemia may alter the normal balance between free and bound drug (2) .Charcoal treatment of uremic sera appears to correct the binding defect (3), however, hemodialysis does not (4). The failure of hemodialysis to correct this defect suggests either that high-affinity, binding inhibitors or middle to high-molecular weight compounds may be responsible for altered drug-protein binding. The addition of supposed "uremic toxins" to normal serum induces a binding abnormality consistent with that seen in end-stage renal disease (ESRD) patients (5,6).

Recently, we reported that low-dose antibiotic therapy was effective in CAPD-related peritonitis (14). To investigate the contribution that altered binding may have made to this observation, the study reported herein examined serum and dialysate protein binding of cefamandole -an acidic cephalosporin antibiotic, in CAPO patients, chronic hemodialysis patients and healthy volunteers. In addition, drug binding in dialysate of CAPO patients was studied in the presence and absence of peritonitis.

KEY WORDS: CAPO; Protein binding; Peritonitis.






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