title: Pharmacokinetics and biotransformation of mirtazapine in human volunteers.
abstract: This paper investigated the pharmacokinetics and biotransformation of mirtazapine in healthy human volunteers. The results showed that the area under the plasma drug concentration-time curve (AUC) of mirtazapine in human plasma appeared to be three times higher than the AUC of demethylmirtazapine. As mirtazapine is marketed as a racemic mixture and both enantiomers possess pharmacological properties essential for the overall activity of the racemate, the pharmacokinetics of mirtazapine were examined and appeared to be enantioselective. The R(-)-enantiomer showed the longest elimination half-life from plasma. This was ascribed to the preferred formation of a quaternary ammonium glucuronide of the R(-)-enantiomer. This glucuronide may be deconjugated, leading to a further circulation of the parent compound, thus causing a prolongation in the elimination half-life. The S(+)-enantiomer was preferentially metabolised into an 8-hydroxy glucuronide. Other metabolic transformation pathways found for mirtazapine were demethylation and N-oxidation. Mirtazapine was extensively metabolised and almost completely excreted in the urine (over 80%) and faeces within a few days after oral administration.
authors: Department of Drug Metabolism & Kinetics, N.V. Organon, Oss, The Netherlands.
authors: L P
authors: LP
authors: Delbressine
authors: M E
authors: ME
authors: Moonen
authors: F M
authors: FM
authors: Kaspersen
authors: G N
authors: GN
authors: Wagenaars
authors: P L
authors: PL
authors: Jacobs
authors: C J
authors: CJ
authors: Timmer
authors: J E
authors: JE
authors: Paanakker
authors: H J
authors: HJ
authors: van Hal
authors: G
authors: G
authors: Voortman