[Cefpiramide, a new cephalosporin with high hepatic elimination; experimental evaluation of its biliary passage and disposition in the liver].
The biliary elimination and hepatic disposition of cefpiramide were studied using an isolated and perfused rabbit liver model. Five experiments were performed, each lasting 3 hours. After addition of 10 mg of cefpiramide to the circulating blood, the biliary concentration reached a mean peak of 741 +/- 15 micrograms/ml between the 30th and 60th minute; the cumulated biliary elimination of the drug amounted 4042 +/- 1099 micrograms, corresponding to 40.4% of the injected dose. The hepato-biliary clearance was 54.5 ml/hr and the biliary elimination rate constant 0.2019(hr-1). At the end of the perfusion, 21.7% of the dose was still present in the circulating blood and 1.4% is found in the liver. Control experiments showed that 36.2% of the cefpiramide added into the experimental device was submitted to degradation. Thus, it was possible to calculate the rate of liver biotransformation of cefpiramide, which accounted for 0.3%. These experimental results confirm the major role of the liver in the elimination of cefpiramide and prove that the drug is not submitted to hepatic metabolisation.
Département de Médecine Interne de la Clinique Médicale B, Centre Hospitalier Universitaire, Strasbourg.
J M
JM
Brogard
J F
JF
Blickle
M
M
Adloff
F
F
Jehl
H
H
Monteil
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D001652:Bile Ducts / Q000378:metabolism*; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D011817:Rabbits
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C036666:cefpiramide
Le cefpiramide, nouvelle céphalosporine à forte élimination hépatique; évaluation expérimentale de son passage biliaire et de sa disposition au niveau du foie.