Diethylpropion [Tenuate Dospan]
Disposition in the Body.
Readily absorbed after oral administration. Metabolised by N-dealkylation, reduction, deamination, and N-hydroxylation primarily to active metabolites; keto reduction is stereoselective resulting in the formation of threo–hydroxylated metabolites; glucuronide formation also occurs along with the formation of hippuric and mandelic acids. About 80 to 90% of a dose is excreted in the urine; the amount excreted in the urine is reduced when the urine is alkaline; of the urinary excreted material, N-ethylaminopropiophenone, norephedrine (phenylpropanolamine), and hippuric acid are the main metabolites together with small amounts of unchanged drug, aminopropiophenone, N-diethylnorephedrine, and N-ethylnorephedrine. Diethylpropion crosses the blood–brain barrier and the placenta. The drug and its metabolites are distributed into breast milk.
Following a single oral dose of 75 mg to 5 subjects, a mean peak plasma concentration of 0.007 mg/L was attained in 0.5 h; total concentrations of the monodesethyl and didesethyl metabolites reached an average peak of 0.19 mg/L at 2 h. [G. J. Wright et al.,Drug Metab. Rev.,1975, 4, 267–276.]
The estimated minimum lethal doses are 200 mg for a child and 2 g for an adult.
The following disposition was reported in a case of fatal overdose resulting from the injection of illicit diethylpropion tablets: blood 5.4 mg/L, bile 14.4 mg/L, kidney 0.9 μg/g, liver 0.9 μg/g, injection site 43.2 μg/g. [R. R. Fysh and J. F. Taylor,Bull. Int. Assoc. Forensic Toxicol.,1978, 142, 16–17.]
Derived from urinary excretion data, 1.5 to 3 h in subjects whose urines are acidic.