@article { WOS:000166516000010,
	title = {Ursodeoxycholic acid modulates cyclosporin A oral absorption in liver transplant recipients},
	journal = {FUNDAMENTAL \& CLINICAL PHARMACOLOGY},
	volume = {14},
	number = {6},
	year = {2000},
	note = {51st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases, SAN DIEGO, CA, MAY 21-22, 2000},
	month = {NOV-DEC},
	pages = {601-609},
	publisher = {Amer Assoc Study Liver Dis},
	type = {Article; Proceedings Paper},
	address = {COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA},
	abstract = {The aim was to study the ursodeoxycholic acid (UDC) effect on thr cyclosporin A (CsA) pharmacokinetics after oral administration of the microemulsion Formulation Neoral(R) (CsA-ME) in liver transplant recipients, and test the potential protective effect of this bile acid 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 late 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 gamma -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. (C) 2000 Editions scientifiques et medicales Elsevier SAS.},
	keywords = {cyclosporin pharmacokinetics, liver transplantation, mathematical modelling, Ursodeoxycholic Acid},
	issn = {0767-3981},
	doi = {10.1111/j.1472-8206.2000.tb00446.x},
	author = {Caroli-Bose, FX and Iliadis, A and Salmon, L and Macheras, P. and Montet, AM and Bourgeon, A and Garraffo, R and Delmont, JP and Montet, JC}
}
