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) as a single i.v. dose containing 100 mg Fe. The average predose concentration was 35.7 +/- 12.5 mumol/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 mumol/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 (AUC) was 1491 mumol/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 (Vc) was 3.21, hence close to the volume of the serum; the volume of distribution at steady state (Vdss) was 7.31; and the volume of distribution during elimination (Vdarea) 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.
Danielson
B G
BG
Department of Medicine, University Hospital, Uppsala, Sweden.
Salmonson
T
T
Derendorf
H
H
Geisser
P
P
D000328:Adult; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000378:metabolism; D013054:Spectrophotometry, Atomic; D013395:Sucrose / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D014168:Transferrin / Q000378:metabolism
D005290:Ferric Compounds; D011990:Receptors, Transferrin; D014168:Transferrin; D013395:Sucrose; D007501:Iron; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid