7432-s and Kidney-Failure--Chronic

An assessment was made of the serum protein binding of representative oral cephems (cefdinir, cefixime and ceftibuten) for sera from healthy subjects (HS) and patients with chronic renal failure (CRF) using an application of equilibrium dialysis under a same set of conditions in vitro. The protein binding capacity of oral cephems in CRF patients being treated with continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD) was significantly less than that in HS, and a marked increase in free drug concentration was observed. While examining the protein binding of oral cephems with heparin in patients on HD, binding capacity decreased significantly immediately following the completion of dialysis compared to that prior to dialysis. On the other hand, the protein binding of oral cephems did not change when used nafamostat mesilate as an anticoagulant. The addition of palmitic acid (PA), a common non-esterified fatty acid (NEFA), to pooled sera from HS caused the binding capacity of oral cephems to decrease, accompanied by increase in PA concentration. It appears from these findings that changes in the binding capacity of oral cephems with HD have possibly been caused by increase in NEFA due to activation of lipase when heparin was used as an anticoagulant. In conclusion, changes in the protein binding capacity of oral cephems in CRF patients should be taken into consideration in attempts to avoid possible side effects.

Topics: Carrier Proteins; Cefdinir; Cefixime; Cefotaxime; Ceftibuten; Cephalosporins; Humans; Kidney Failure, Chronic; Palmitic Acid; Palmitic Acids; Renal Dialysis

The impact of renal insufficiency on the dispositions of 300 mg of orally administered ceftibuten-cis, a new broad-spectrum oral cephalosporin, and its primary metabolite ceftibuten-trans was characterized in 30 adult subjects. Subjects were divided into five groups of six subjects each on the basis of their 24-h ambulatory creatinine clearances (CLCR). The apparent total body clearance (CLP/F; where F is absolute bioavailability) and renal clearance of ceftibuten-cis were significantly lower in subjects with end-stage renal disease (on maintenance hemodialysis; group V) and in those with severe (CLCR, 5 to 29 ml/min; group IV) and moderate (CLCR, 30 to 49 ml/min; group III) renal insufficiency than in those with mild renal insufficiency (CLCR, 50 to 80 ml/min; group II) or normal renal function (CLCR, greater than 80 ml/min; group I). A significant correlation was observed between CLCR and ceftibuten-cis CLP/F. The mean apparent steady-state volume of distribution (V beta/F) of ceftibuten-cis ranged from 0.21 to 0.24 liter/kg in subjects in group I, II, III, and IV. V beta/F was significantly greater in the group V subjects with end-stage renal disease (V beta/F, 0.39 +/- 0.27 liters/kg). These changes in V beta/F cannot be separated from possible changes in bioavailability. The maximum concentration of ceftibuten-trans in plasma was significantly higher and occurred significantly later in group IV subjects than it did in subjects in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Biological Availability; Ceftibuten; Cephalosporins; Chromatography, High Pressure Liquid; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Stereoisomerism