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.
Demontes-Mainard
F
F
Centre de Pharmacologie, EA DRED 525, Hôpital Pellegrin, Bordeaux, France.
Vinçon
G
G
Labat
L
L
Amouretti
M
M
Necciari
J
J
Kieffer
G
G
Bannwarth
B
B
D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000378:metabolism*; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002779:Cholestasis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011485:Protein Binding
D001798:Blood Proteins; D002511:Cephalosporins; C036666:cefpiramide