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

Gut. 1989 Mar;30(3):391-6. doi: 10.1136/gut.30.3.391.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Administration, Oral
  • Adult
  • Bile / physiology
  • Biliary Tract / physiology*
  • Biological Availability
  • Constriction
  • Cyclosporins / administration & dosage
  • Cyclosporins / pharmacokinetics*
  • Female
  • Humans
  • Infusions, Intravenous
  • Liver / physiopathology
  • Liver Function Tests
  • Liver Transplantation*
  • Male
  • Middle Aged

Substances

  • Cyclosporins