CEFPIRAMIDE KINETICS AND PLASMA-PROTEIN BINDING IN CHOLESTASIS

Cefpiramide is a new parenteral cephalosporin mainly excreted in the b ile. 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 ultraf iltration. 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 sub jects. As a result, the terminal elimination half-life was longer in p atients (12.0 +/- 2.9 h vs 5.3 +/- 0.9 h). Owing to impaired biliary e limination of cefpiramide in cholestasis, the urinary recovery of unch anged drug in patients was about five times greater than in healthy su bjects (85.1 +/- 10.3 % vs 16.2 +/- 3.9%). Plasma binding was signific antly lower in cholestasis (fu = 0.23 +/- 0.13 vs 0.02 +/- 0.004 in he althy subjects). Accordingly, the dosage regimen of cefpiramide should be modified in patients with cholestasis.