Cyclosporin A pharmacokinetics in liver transplant recipients in relation to biliary T-tube clamping and liver dysfunction.
Cyclosporin A pharmacokinetics were studied after oral (4-14 mg/kg body weight) and intravenous dosing (1.5-3.5 mg/kg) in 13 orthotopic liver transplant recipients before and after permanent clamping of the biliary T-tube. After T-tube clamping, cyclosporin A absorption was faster and more complete with the mean time of peak concentration, tmax, reduced to around three hours from around six hours and mean bioavailability rising from only 16.6% (n = 13) to 30% in the entire group (n = 11 after clamping) or to 35% after excluding two patients who developed severe cholestasis after the preclamping study. Bioavailability in these two patients fell below 8% and to around 1% in a further patient with severe graft dysfunction. Clamping reduced the metabolic clearance of cyclosporin A by only 25% from a mean before clamping of 2.9 ml/min/kg to 2.3 ml/min/kg (n = 11). Oral cyclosporin A becomes a reliable means of maintaining therapeutic drug concentrations only after bioavailability increases in association with T-tube clamping and in the absence of severe liver dysfunction or cholestasis.
Naoumov
N V
NV
Liver Unit, King's College Hospital, Denmark Hill, London.
Tredger
J M
JM
Steward
C M
CM
O'Grady
J G
JG
Grevel
J
J
Niven
A
A
Whiting
B
B
Williams
R
R
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D001646:Bile / Q000502:physiology; D001659:Biliary Tract / Q000502:physiology*; D001682:Biological Availability; D003250:Constriction; D003524:Cyclosporins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008099:Liver / Q000503:physiopathology; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged
D003524:Cyclosporins