[Cyclosporin A metabolism and induction of cytochrome P-450 in orthoptic hepatic transplantation in rats].
The aim of our study were 1) to establish that cyclosporin (CsA) metabolism was correlated with the rate of cytochrome P4503A (cyt.) in Wistar rats induced with dexamethasone (Dex.), 2) to demonstrate that the induction of cyt. with Dex. in liver "rat donor" was transmissible to "recipient rat" after liver transplantation. Sixty rats were divided in 5 groups. In group T, a single dose of CsA (10 mg/kg) was administered intravenously in 10 rats; in group D, 10 rats were treated with Dex (300 mg/kg daily for 4 days) and then received CsA as above; in group BN 5 rats were treated with beta-naphthoflavone. Thirty five rats underwent a liver transplantation either from "non induced donors" (group G, n = 11) or from "induced donors with Dex." (group GD, n = 24) followed by CsA injection the next day. For each rat, CsA plasma levels were determined by radioimmunoassay in 6 samples. Liver microsomes cyt. from samples of the liver of donor rats (group G and GD) or after sacrifice (group T, D, BN) were quantitated by immunoblot analysis and estimated from densitometric analysis of the blot. Mean maximal plasma concentration (Cmax) were 2,822 +/- 997 ng/ml in group T, 1,447 +/- -458 ng/ml in group D, 2,685 +/- 1,383 ng/ml in group G, 1,337 +/- 713 ng/ml in group GD and 3,094 +/- 685 ng/ml in group BN. Considering the Cmax and the ASC (area under curve), there was a significant difference between all groups and separately between groups T and D, G and GD.(ABSTRACT TRUNCATED AT 250 WORDS)
Fabre
J M
JM
Service de Chirurgie C, Hôpital Saint-Eloi, Montpellier.
Pedrosa
R
R
Bonardet
A
A
Pichard
L
L
Descomps
B
B
Domergue
J
J
Baumel
H
H
Maurel
P
P
D000818:Animals; D016572:Cyclosporine / Q000097:blood / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage; D004790:Enzyme Induction; D016031:Liver Transplantation; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D014184:Transplantation, Homologous
D003907:Dexamethasone; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System
Métabolisme de la ciclosporine A, et induction du cytochrome P450 dans la transplantation hépatique orthotopique chez le rat.