Cefpiramide kinetics and plasma protein binding in cholestasis

Cefpiramide is a new parenteral cephalosporin mainly excreted in the bile. Eight patients with cholestasis and 11 healthy subjects received a single 1 g i.v. dose. Cefpiramide concentrations in plasma and urine were measured by h.p.l.c. and plasma binding was determined by ultrafiltration. Total clearance of cefpiramide (mean +/‐ s.d.) was 15.5 +/‐ 7.1 ml min‐1 in patients and 25.6 +/‐ 4.6 ml min‐1 in healthy subjects. As a result, the terminal elimination half‐life was longer in patients (12.0 +/‐ 2.9 h vs 5.3 +/‐ 0.9 h). Owing to impaired biliary elimination of cefpiramide in cholestasis, the urinary recovery of unchanged drug in patients was about five times greater than in healthy subjects (85.1 +/‐ 10.3% vs 16.2 +/‐ 3.9%). Plasma binding was significantly lower in cholestasis (fu = 0.23 +/‐ 0.13 vs 0.02 +/‐ 0.004 in healthy subjects). Accordingly, the dosage regimen of cefpiramide should be modified in patients with cholestasis.