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The Pharmacokinetics and Liver Metabolism of N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA) in Rats

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 Sci. 1994;54(26):PL519-24.

PMID: 8208060

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP114562593	(±)-N-Hydroxy-3,4-methylenedioxyamphetamine		114562-59-3	Price

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