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Clinical Pharmacokinetics

, Volume 58, Issue 2, pp 213–222 | Cite as

Evaluation of the Interaction of Amino Acid Infusion on 177Lu-Dotatate Pharmacokinetics in Patients with Gastroenteropancreatic Neuroendocrine Tumors

  • Alicja Puszkiel
  • Mathilde Bauriaud-Mallet
  • Roxane Bourgeois
  • Lawrence Dierickx
  • Frédéric Courbon
  • Etienne ChatelutEmail author
Original Research Article

Abstract

Background and Objective

177Lu-Dotatate is a radio-labeled analog of somatostatin used in the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. In order to prevent nephrotoxic effects of 177Lu-Dotatate a co-infusion of amino acids (AA) is administered, resulting in a decrease in tubular renal reabsorption of 177Lu-Dotatate. This study aimed to quantify the impact of AA co-infusion on the pharmacokinetics of 177Lu-Dotatate in cancer patients and to evaluate its relationship with toxicity during the first treatment cycle (C1).

Methods

7.4 GBq of 177Lu-Dotatate was administered to 42 patients over a 30-min intravenous infusion. Infusion of AA started 2 h before and continued for 6 h after the infusion of 177Lu-Dotatate. Radioactivity–time data (n = 346) were analyzed using NONMEM® (version 7.2.0).

Results

177Lu-Dotatate pharmacokinetics was best described by a three-compartment model with first-order elimination. AA co-infusion had a significant effect (‘fixed effect’) on 177Lu-Dotatate pharmacokinetics, with a mean value of 1.5-fold (95% confidence interval 1.03–1.97) increase in the elimination rate constant (k10) from 0.204 to 0.306 h−1, but this AA co-infusion effect was associated with a large inter-individual variability (IIV) of 104%. The individual k10 values increased during concomitant AA infusion by a factor ranging from 1.01 to 21.3 for 27 patients, whereas the opposite effect was observed in 15 patients (range 0.36–0.99) of whom seven had a k10 value lower than 0.85. This variability in AA effect contributed to the variability in 177Lu-Dotatate plasma exposure (area under the concentration–time curve from time zero to Day 15 for C1 [AUCDay15]) that correlated with lymphopenia observed at Day 15 (p = 0.004).

Conclusions

A substantial effect of AA co-infusion on 177Lu-Dotatate pharmacokinetics was shown but was associated with high IIV, contributing to IIV in hematological toxicity.

Notes

Compliance with ethical standards

The study was conducted in compliance with ethical standards.

Conflict of interest

Alicja Puszkiel, Mathilde Bauriaud-Mallet, Roxane Bourgeois, Lawrence Dierickx, Frédéric Courbon, and Etienne Chatelut declare that they have no conflict of interest.

Funding

No specific funding was received for either carrying out the study or preparing the manuscript.

Supplementary material

40262_2018_674_MOESM1_ESM.docx (20 kb)
Supplementary material 1 (DOCX 19 kb)

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institut Claudius-RegaudInstitut Universitaire du Cancer Toulouse-OncopoleToulouseFrance
  2. 2.CRCT, Cancer Research Center of Toulouse, Inserm U1037Université Paul Sabatier, IUCT-OncopoleToulouseFrance
  3. 3.Department of RadiopharmacyInstitut Universitaire du Cancer Toulouse-OncopoleToulouseFrance
  4. 4.Department of Medical ImagingInstitut Universitaire du Cancer Toulouse-OncopoleToulouseFrance

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