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1. Less than 5% of a dose of the conventional oral formulation of cyclosporin, Sandimmun, is absorbed in liver transplant recipients with external biliary drainage, necessitating intravenous administration of the drug and exposing the patient to increased risk of severe side-effects. 2. We compared the pharmacokinetics of the conventional oral formulation of cyclosporin with that of the new microemulsion formulation, Neoral, in eight liver transplant recipients with external biliary diversion. Patients were maintained on a continuous infusion of cyclosporin until steady-state conditions had been achieved. They were then given a test dose (10 mg kg-1) of either the conventional or microemulsion formulation (randomised order) followed by the same dose of the other formulation. Parent cyclosporin concentrations were measured in whole blood samples collected at timed intervals over the 24 h after the oral doses and pharmacokinetic parameters calculated. 3. The bioavailability of cyclosporin from the microemulsion formulation was, on average, 6.5-fold (95% C.I. 1.9 to 11.1-fold) greater than that of the conventional formulation, indicating the improved absorption characteristics of the new oral microemulsion formulation during external bile drainage. 4. A significant negative correlation was found between the external bile drainage volume and bioavailability of cyclosporin from the microemulsion formulation (r = -0.8; P = 0.016), suggesting that variability in cyclosporin absorption from the microemulsion formulation may still be at least partly attributable to bile- dependence.(ABSTRACT TRUNCATED AT 250 WORDS)
A K Trull, and
K K Tan, and
L Tan, and
G J Alexander, and
N V Jamieson
January 1995,
Transplant international : official journal of the European Society for Organ Transplantation,
A K Trull, and
K K Tan, and
L Tan, and
G J Alexander, and
N V Jamieson
July 1996,
Transplantation,
A K Trull, and
K K Tan, and
L Tan, and
G J Alexander, and
N V Jamieson
January 2000,
Fundamental & clinical pharmacology,
A K Trull, and
K K Tan, and
L Tan, and
G J Alexander, and
N V Jamieson
August 1996,
Transplantation,
A K Trull, and
K K Tan, and
L Tan, and
G J Alexander, and
N V Jamieson
January 1997,
Transplantation proceedings,
A K Trull, and
K K Tan, and
L Tan, and
G J Alexander, and
N V Jamieson
August 1999,
Pediatric transplantation,
A K Trull, and
K K Tan, and
L Tan, and
G J Alexander, and
N V Jamieson
August 1998,
Transplantation proceedings,
A K Trull, and
K K Tan, and
L Tan, and
G J Alexander, and
N V Jamieson
August 1998,
Transplantation proceedings,
A K Trull, and
K K Tan, and
L Tan, and
G J Alexander, and
N V Jamieson
January 1996,
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association,
A K Trull, and
K K Tan, and
L Tan, and
G J Alexander, and
N V Jamieson
March 2004,
Transplantation proceedings,
