The pharmacokinetics and liver metabolism of N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA) in rats.
W R Ravis, A K Valaer, D Brzozowski, C R Clark
Life Sciences 1994 DOI: 10.1016/0024-3205(94)00726-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal pharmacokinetic study (in vitro liver slice and in vivo intravenous dosing) Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | N-OH MDA |
| Dose | 15 mg/kg |
| Duration | 2-hour liver slice incubation; plasma sampling after intravenous dose |
| Key points | N-OH MDA is rapidly converted to MDA in rats: approximately 85% was biotransformed in liver slices within 2 hours, and after intravenous dosing N-OH MDA had a plasma half-life of 0.86 minutes while MDA peaked at 8 minutes with a half-life of 1.68 hours. |
Abstract
The metabolism and disposition of N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA) was studied by utilizing rat liver slices as well as by intravenous pharmacokinetic studies in rats. In the liver slice experiments, N-OH MDA (16 micrograms/ml) was incubated with rat liver slices and the disappearance of N-OH MDA and the appearance of MDA were observed over 2 hours. Drug and metabolites were assayed by a reverse phase high performance liquid chromatographic procedure including a C8 column and UV detection. N-OH MDA disappeared from the plasma at an apparent first-order rate with a t1/2 of 36.3 +/- 8.4 min. By the end of 2 hours, approximately 85% of the N-OH MDA was biotransformed to MDA. Following placement of jugular cannulas in rats, a dose of 15 mg/kg of N-OH MDA was administered intravenously. With rapid blood sampling, a t1/2 of 0.86 +/- 0.12 min was observed for N-OH MDA. A total body clearance of 9.09 +/- 2.06 L/hr/kg and a volume of distribution of 0.184 +/- 0.022 L/kg were noted. Plasma concentrations of MDA were observed after the N-OH MDA dose to rats. The MDA t1/2 after N-OH MDA dosing was 1.68 +/- 0.29 hours with peak plasma concentrations at 8 min. No other major metabolites could be detected in liver slice, plasma, or urine samples. Both sets of studies demonstrate the rapid conversion of N-OH MDA to MDA in rats.