Cyclosporin A pharmacokinetics in liver transplant recipients in relation to biliary T-tube clamping and liver dysfunction

Abstract

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.