Metabolism of dimetindene in rats.

The preparative separation of dimetindene (CAS 5636-83-9) enantiomers was achieved by fractionated crystallization of the diastereomeric tartrate salts. HPLC on alpha-AGP (alpha 1-acid glycoprotein) was used for confirmation of the enantiomeric purity. After administration of the enantiomers to rats the AUC and Cmax of S(+) dimetindene and (-)N-demethyldimetindene were slightly increased.

Quantification of dimethindene in plasma by gas chromatography-mass fragmentography using ammonia chemical ionization.

A gas chromatographic-mass fragmentographic method using ammonia chemical ionization for the determination of dimethindene in human plasma is described. The drug was isolated from plasma by liquid-liquid extraction with hexane-2-methylbutanol. Plasma components were separated on a capillary column coated with chemically bonded methyl silicone.

High-performance liquid chromatographic method for the determination of dimethindene in urine.

An automated high-performance liquid chromatographic assay, using on-line solid-phase extraction, is described for the determination of dimethindene in urine. The solid-phase extraction of the sample (1000 microliters) and the elution of the drug on to the analytical column are performed automatically and concomitantly. The limit of quantification is 5 pmol/ml.

Pharmacokinetic study of 14C-letosteine in man after oral intake and steady-state.

Based on previous animal and on preliminary human results a further human study was performed in order to confirm the relevant pharmacokinetic parameters and the lack of accumulation of letosteine after repeated administrations. Thus, six healthy male volunteers were given a single oral dose of 50 mg (100 microCi) 14C-letosteine in form of gelatine capsules. A treatment lasting 11 days to obtain a steady-state was started three days later with three similar daily oral doses of unlabelled letosteine.