Organ Distribution and Clearance of (3,4)-Methylenedioxypyrovalerone (MDPV) Enantiomers in Female and Male Rats after Intravenous Administration of Racemic MDPV

The objective of these studies was to characterize the organ distribution and clearance of ( S )‐ and ( R )‐MDPV in female and male Sprague Dawley rats after administration of ( R,S )‐MDPV, hypothesizing that there would be enantiomer and sex dependent differences in organs most relevant to MDPV pharmacology such as the brain, heart, and liver. After administration of an intravenous 3 mg/kg dose of ( R,S )‐MDPV, male and female rats (n=4–5/time point of collection/sex) were euthanized, and blood, brain, kidney, liver, heart, and spleen were rapidly collected at 5, 20, 60, 90, and 120 min after dosing. ( S )‐ and ( R )‐MDPV enantiomers were quantified in serum and homogenized organs by a chiral liquid chromatography tandem mass spectrometry technique. While substantial concentrations of both enantiomers accumulated in kidney tissue of both sexes, unchanged renal clearance was only a minor contributor to MDPV total body clearance (0.6 – 1.5%). These data indicated that MDPV metabolic clearance was the major route of elimination of unchanged MDPV. In the liver, concentrations of both enantiomers were substantially lower than in the kidney, and, interestingly, there were significantly (p<0.05) lower liver concentrations of ( S )‐ than ( R )‐MDPV in both sexes. These data indicated that the liver had a higher intrinsic metabolic clearance for the ( S )‐enantiomer than the ( R )‐enantiomer. This may also explain why the blood concentrations of ( R )‐MDPV were consistently higher than the concentrations of ( S )‐MDPV. There was a time‐dependent increase in the ratio of the more potent ( S )‐ compared to ( R )‐enantiomer in the brain and heart in both sexes. Also, measures of brain concentrations of both enantiomers were significantly (p<0.05) elevated in male compared to female rats. In conclusion, renal clearance of unchanged MDPV was insubstantial in both sexes. Clearance of MDPV was predominantly metabolic with the liver preferentially eliminating ( S )‐MDPV. Additionally, the brain and heart S/R enantiomeric ratio showed significant (p<0.05) increases over time in male and female rats. This may contribute to ( S )‐MDPV having greater potency than ( R )‐MDPV at sites of action in these two organs. Support or Funding Information Funded by NIDA grants DA039195 and T32 GM106999 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .