Pharmacokinetics of BMEDA after Intravenous Administration in Beagle Dogs

Chih-Hsien Chang,Te-Wei Lee,Si-Yen Liu

doi:10.3390/molecules19010538

Chih-Hsien Chang, Te-Wei Lee + Show 1 more

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https://doi.org/10.3390/molecules19010538

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Abstract

The pharmacokinetics of N,N-bis(2-mercapatoethly)-N',N'-diethylenediamine (BMEDA), a molecule that can form a chelate with rhenium-188 (188Re) to produce the 188Re-BMEDA-liposomes, was studied. In this work, beagles received a single injection of BMEDA, at doses of 1, 2, or 5 mg/kg; the concentration of BMEDA in the beagles’ plasma was then analyzed and determined by liquid chromatography-mass spectrometry/mass spectrometry. Based on the pharmacokinetic parameters of BMEDA, we found that male and female animals shared similar patterns indicating that the pharmacokinetics of BMEDA is independent of gender differences. In addition, the pharmacokinetics of BMEDA was seen to be non-linear because the increase of mean AUC0–t and AUC0–∞ values tend to be greater than dose proportional while the mean Vss and CL values of BMEDA appeared to be dose dependent. The information on the pharmacokinetics of BMEDA generated from this study will serve as a basis to design appropriate pharmacology and toxicology studies for future human use.

Highlights

Colorectal cancer is the third most common cancer and the fourth most common cause of cancer mortalities worldwide [1,2]
The purpose of this study is to evaluate the pharmacokinetics of BMEDA in beagle dogs via single intravenous injection administration
Selectivity was confirmed through the chromatograms of blank samples and blank samples spiked with BMEDA

Summary

Introduction

Colorectal cancer is the third most common cancer and the fourth most common cause of cancer mortalities worldwide [1,2]. While various treatment regimens and cancer drugs are available for colorectal cancer, a variety of new treatments for this cancer are being developed [3,4], one of which includes the use of nanotechnology [5]. Rhenium-188 (188Re) is an ideal radionuclide for therapeutic use because of its maximum beta emission of 2.12 MeV and 155 keV gamma emission used for therapeutics and for imaging, respectively. It has a short physical half-life of 16.9 h [11]. Further clinical applications of 188Re-BMEDA-liposome would first require an evaluation of its safety through animal models

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