Impact of co-administration of two amino acid solutions on the elimination and adverse effects of 177Lu-Dotatate

¹⁷⁷Lu-Dotatate is a somatostatin analog prescribed to treat neuroendocrine tumours. Plasma concentrations of ¹⁷⁷Lu-Dotatate in 83 patients were used to build a population pharmacokinetic model and estimate its pharmacokinetic parameters. Amino acid infusion is associated to decrease the nephrotoxicity of ¹⁷⁷Lu-Dotatate. We compared the impact of two amino acid solutions (Primene® which a mixed of 20 amino-acids and Lysakare® composed of only Arginine and Lysine) on pharmacokinetics of ¹⁷⁷Lu-Dotatate. Lysakare® does not increase the elimination of ¹⁷⁷Lu-Dotatate on average, unlike Primene®. However, for both solutions there is an inter-individual variability in both the impact of the amino acid solution and the elimination of ¹⁷⁷Lu-Dotatate. A relationship between ¹⁷⁷Lu-Dotatate exposure and treatment-induced lymphopenia was also observed.

The systemic exposure of each patient could be an additional parameter to consider in the individualised management of patients treated with ¹⁷⁷Lu-Dotatate. Population pharmacokinetic methodology may lead to a better understanding of both the efficacy and toxicity of this therapeutic modality.

These results open up a new avenue of research and offer the possibility of individually tailoring ¹⁷⁷Lu-Dotatate administration for this indication justified by the large pharmacokinetic interindividual variability associated with a limited intrapatient variability of this radiolabeled compound.