Preclinical pharmacokinetics, biodistribution, excretion, and plasma protein binding study of ⁵⁸Fe-labeled hemin by...

Hemin, a stable form of heme iron, is a potential iron supplement for the treatment of iron deficiency. To date, the pharmacokinetics and in vivo ADME properties of hemin are to be elucidated.

In this study, a rapid, sensitive, and validated inductively coupled plasma mass spectrometry (ICP-MS) method was used in combination with ⁵⁸Fe stable isotope labeling to systemically investigate the plasma pharmacokinetics, biodistribution, excretion, and plasma binding profiles of hemin in animals.

Results showed that the ICP-MS method is accurate and sensitive enough to quantitatively determine the in vivo disposition process of ⁵⁸Fe derived from ⁵⁸Fe-labeled hemin. Following intra-gastric administration, ⁵⁸Fe was rapidly absorbed in gastrointestinal tract, with C_max of 41.1 ± 23.1 ng/mL, T_max of 1.38 ± 0.48 h, and bioavailability of 1.12 ± 0.45 % in beagle dogs. Moreover, ⁵⁸Fe was distributed to various organs including stomach, small intestine, spleen, and liver, within a few hours after intra-gastric administration in rats. Excretion of ⁵⁸Fe in rats was predominantly via feces (76.3 ± 15.1 % of dosage), whereas minimally via urine (0.14 ± 0.08 % of dosage). Protein binding study revealed majority of ⁵⁸Fe in plasma was bound to proteins, with average binding rates of 81.0 % and 92.7 % in human and rat plasma, respectively.

In conclusion, the present study validated the work-flow of preclinical pharmacokinetic studies of iron-containing drug candidates with using ICP-MS and stable (trace) isotope labeling strategy. It also provided useful information to support the further development of hemin as a drug/nutrition supplement candidate.