Pharmacokinetics of BMEDA after intravenous administration in beagle dogs

• Published in: Molecules (Basel, Switzerland) Vol. 19; no. 1; pp. 538 - 549
• Main Authors: Chang, Chih-Hsien, Liu, Si-Yen, Lee, Te-Wei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.01.2014; MDPI
• Subjects: 188Re-BMEDA-liposome; acute toxicity; Administration, Intravenous; Animals; BMEDA; Cancer therapies; Chromatography, Liquid; Colorectal cancer; Dogs; Dosimetry; Drug dosages; Ethylenediamines - administration & dosage; Ethylenediamines - pharmacokinetics; Female; Gender differences; Liposomes; Male; Mass spectrometry; Organometallic Compounds - administration & dosage; Organometallic Compounds - pharmacokinetics; Pharmacokinetics; Plasma; Radiation; radiopharmaceutical; Regression analysis; Reproducibility of Results; Scientific imaging; Tandem Mass Spectrometry; Toxicity; Toxicology; Tumors; Taiwan
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules19010538

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.