Pharmacokinetic interpretation of FK 506 levels in blood and in plasma during a European randomised study in primary liver transplant patients. The FK 506 European Study Group.

The efficacy and safety of FK 506 compared with cyclosporin were evaluated in a European multicentre study with primary liver transplant patients. The daily intravenous doses ranged from 0.15 to 15.9 mg and the daily oral doses from 0.5 to 30 mg. Trough concentrations of FK 506 in blood and plasma were determined by an enzyme immunoassay. Blood concentrations ranged from 0.5 to 391 ng/ml and from 0.5 to 616 ng/ml after intravenous and oral doses, respectively. The corresponding plasma levels ranged from 0.05 to 56 ng/ml and from 0.05 to 104 ng/ml, respectively. In comparison to the parallel US trial, the mean oral doses in this European study were about 20% lower and the mean blood concentrations were 40% lower. However, the efficacy in these two trials was similar. No significant relationship between blood levels and selected adverse events or serum creatinine concentrations were observed in the European study (6-month data). An analysis of plasma protein and albumin concentrations showed an increase to normal ranges 4-8 weeks post-transplantation. The level of both markers remained lower in patients who withdrew due to adverse events.