Chronopharmacokinetics of Cyclosporine A in the Wistar rat following oral administration.
The pharmacokinetics of Cyclosporine A (CsA) was studied in male Wistar rats weighting 300 +/- 50 g trained to a 12:12 light-dark cycle. Oral administration (40 mg/kg) was performed at 1 of 4 different temporal stages: 09.00 h, 15.00 h, 21.00 h or 03.00 h (local time) i.e. 0200, 0800, 1400 or 2000 HALO (hours after light on). Blood samples were collected over 72-96 h after dosing, plasma was separated by centrifugation at 37 degrees C and stored frozen until assay, using radioimmunoassay (RIA). Two experiments were performed: the first with 4 groups of 48 rats and a non-specific polyclonal antibody (P-RIA); and the second with only 2 groups of 48 rats and a more specific monoclonal antibody (M-RIA). Plasma concentration data were evaluated with model-based linear pharmacokinetic concepts, with apparent zero-order or first-order absorption and n-exponential disposition (n = 1, 2 or 3): models MN0 or MN1. A compartment-independent approach was also conducted and led to area under the plasma concentration-time curve (AUC) and mean residence time (MRT) determinations. A comparison of the pharmacokinetic profiles across time of administration indicates that absorption, first-pass metabolism and tissue distribution of CsA in the rat are circadian-dosing stage dependent.
Malmary
M F
MF
Equipe de Chronopharmacologie, Faculté des Sciences Pharmaceutiques, Toulouse, France.
Kabbaj
K
K
Labat
C
C
Batalla
A
A
Houti
I
I
Moussamih
S
S
Oustrin
J
J
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D016572:Cyclosporine