Effect of hepatic dysfunction and T-tube clamping on FK 506 pharmacokinetics and trough concentrations

In initial clinical trials of organ transplantation, FK 506 has shown remarkable immunosuppressive activity. 1 The drug is very lipophilic, metabolized in the liver, and predominantly eliminated through the bile. 2 Hepatic dysfunction was expected to alter the pharmacokinetics of FK 506. Hepatic dysfunction is also known to alter the absorption of lipid soluble drugs. 3 This is related to the lack of sufficient bile for solubilization of the drug in the gastrointestinal tract. Orthotopic liver transplantation (OLT) commonly reqyires temporary external drainage of bile via T tube. Clamping and unclamping of the T tube allowing bile to be delivered to the gastrointestinal tract or drained externally, respectively, could affect the absorption and bioavailability of lipid soluble FK 506, as it is known to do with CyA. The objectives of this study were to examine the effect of hepatic dysfunction on the pharmacokinetics of FK 506 following intravenous and oral doses, to study the effect of liver dysfunction on the daily trough concentration of the drugs, and to define the effect of T tube clamping and unclamping following OLT on the absorption and bioavailability of the drug.