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Assessment was made on the serum protein binding of clarithromycin (CAM), a representative oral macrolide, using sera from healthy subjects (HS) and patients with chronic renal failure (CRF) applying equilibrium dialysis in vitro. The protein binding of CAM was 81.9 +/- 1.9%, 85.9 +/- 3.6%, 82.9 +/- 3.3% and 86.8 +/- 3.3% for sera from HS, from patients in conservative treatment (ND), from those receiving hemodialysis (HD) and from those with continuous ambulatory peritoneal dialysis (CAPD), respectively. There was no significant difference among these values. The protein binding of CAM was 82.9 +/- 3.3% and 68.8 +/- 3.5% for sera before and after HD, respectively. There was significant difference between these values. In the study of the protein binding in patients on HD at an albumin concentration of 0.5 mM, the protein binding of CAM for sera was found to be significantly decreased following HD as compared to that prior to HD. The addition of palmitic acid (PA), a common NEFA, to pooled sera from HS, the protein binding of CAM showed no change. These findings suggest that changes in the protein binding of CAM with HD have been possibly caused by an increase in a drug binding inhibiter other than NEFA (PA) or by an allosteric effect on the albumin binding capacity. At therapy using CAM, the possibility of enhanced pharmacological effects and increased adverse reactions of CAM due to decreased protein binding in patients on HD should be considered.
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