Τίτλος:
Ursodeoxycholic acid modulates cyclosporin A oral absorption in liver transplant recipients
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The aim was to study the ursodeoxycholic acid (UDC) effect on the cyclosporin A (CsA) pharmacokinetics after oral administration of the microemulsion formulation Neoral® (CsA-ME) in liver transplant recipients, and test the potential protective effect of this bile add on liver and renal CsA-ME-induced toxicity. At entry into the study, 12 patients who underwent orthotopic liver transplantation received CsA-ME, for at least 6 months. They then received a cotreatment CsA-ME plus UDC (13.8 mg·kg-1·day-1) for three months. Blood concentrations of CsA were measured using a monoclonal antibody specific for the parent compound. The kinetic data were analysed by a mathematical model incorporating a time dependent rate coefficient for CsA intestinal absorption, before and after UDC treatment. Changes in serum markers of hepatic and renal injury were assessed. Individual serum bile acids were determined by chromatography. Serum levels of UDC increased from 3 to about 45 % of total serum bile acids after UDC treatment. The estimated model parameters indicate that UDC administration modulates CsA intestinal absorption. In the nine non-cholestatic patients, UDC reduced the absorption rate and the bioavailability of CsA without modifying the elimination rate constant of CsA and the CsA pre-drug levels. In contrast, in the three cholestatic patients, the bioavailability tended to be higher and the absorption rate faster when CsA was combined with UDC. UDC significantly decreased elevated γ-glutamyl transferase and creatinine serum levels and induced some clinical improvements such as disappearance of headaches in four patients. In conclusion, a 3-month UDC treatment modifies CsA intestinal absorption without affecting CsA elimination rate constant. On the other hand, UDC supplementation appears to improve CsA tolerability. © 2000 Éditions scientifiques et médicales Elsevier SAS.
Συγγραφείς:
Caroli-Bosc, F.-X.
Iliadis, A.
Salmon, L.
Macheras, P.
Montet, A.-M.
Bourgeon, A.
Garraffo, R.
Delmont, J.-P.
Montet, J.-C.
Περιοδικό:
Fundamental and Clinical Pharmacology
Εκδότης:
Elsevier Masson SAS
Λέξεις-κλειδιά:
bile acid; creatinine; cyclosporin A; gamma glutamyltransferase; ursodeoxycholic acid, adult; aged; article; bile acid blood level; cholestasis; chromatography; chronotherapy; clinical article; controlled study; creatinine blood level; drug absorption; drug bioavailability; drug blood level; drug effect; drug elimination; drug formulation; drug induced disease; drug mechanism; drug potentiation; drug tolerability; female; gamma glutamyl transferase blood level; human; intestine absorption; kidney injury; liver injury; liver protection; liver transplantation; male; mathematical model; priority journal
DOI:
10.1111/j.1472-8206.2000.tb00446.x
