Pharmacokinetics of iron(III)-hydroxide sucrose complex after a single intravenous dose in healthy volunteers

The pharmacokinetics of iron were investigated after intravenous administration to 12 healthy volunteers of iron(III)-hydroxide sucrose complex (Venofer(R)) as a single i.v dose containing 100 mg Fe. The average predose concentration was 35.7 +/- 12.5 mu mol/l. There was no statistically significant difference between the serum iron level before injection (0 h) and the level at 24 h after the injection. The compartment model used includes a Michaelis-Menten term and is in excellent agreement with the observed exchange of iron to transferrin and with the daily iron turnover by transferrin. The intravenously injected iron(III)-hydroxide sucrose complex led rapidly to high serum iron levels. Maximum measured levels averaged 538 mu mol/l (30.0 mg/l) at 10 min after the injection. The terminal half-life of the injected iron was calculated to be 5.3 h. Mean total area under the curve (AUG) was 1491 rho mol/l h, the mean residence time (MRT) was 5.5 h. The total body clearance was 20.5 ml/min. The volume of distribution of the central compartment (V-c) was 3.21, hence close to the volume of the serum; the volume of distribution at steady state (Vd(ss)) was 7.3 1; and the volume of distribution during elimination (Vd(area) was 9.21. The calculated amount of iron transported by transferrin was 31.0 +/- 6.6 mg Fe/24h. In summary, the data show that the injected iron(III)-hydroxide sucrose complex is quickly cleared from the serum with a terminal half-life of approximately 5-6 h. Renal elimination of iron contributed very little to the overall elimination (in average < 5 %). Renal elimination of sucrose averaged about 68 +/- 10 % and 75 +/- 11 % of the administered dose after 4 h and 24 h, respectively.