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. In agreement with the serum concentration data significantly more (-)N-demethyldimethindene was excreted into urine after administration of the individual enantiomers. S(+) dimetindene was metabolised to a lesser extent in vivo (see above) as well as in vitro in rat liver homogenate. After prior enzyme induction conversion of the enantioselectivity with respect to unmetabolised dimetindene occurred. 6-Methoxydimetindene, 6-hydroxydimetindene and 6-hydroxy-N-demethyldimetindene were synthesized. 6-Methoxydimetindene is likely to be a metabolite since the retention times of synthetic compound and the substance extracted from serum and urine are identical. The formation of 6-hydroxy-N-demethyldimetindene was proved for the first time by comparison of the mass spectra of metabolite isolated from in vitro incubations and synthetic compound after derivatisation with acetic anhydride.

Transdermal absorption of dimethindene in man.

Dimethindene and its metabolite N-demethyldimethindene were determined in human urine after dermal administration of dimethindene. The HPLC-method used was previously described. Data of 8 volunteers are presented. After 32 h an average of 0.023% of the administered dose of dimethindene and 0.022% of N-demethyldimethindene were excreted into urine. Since also after oral administration of dimethindene only about 1% of unmetabolised dimethindene is found in urine it can be concluded that a certain amount of dimethindene is absorbed through the skin after dermal administration.

[Solid phase-sample preparation of ifosfamide and chloroethyl metabolites in biological material. 1. Determination in plasma and urine]. / Festphasen-Probenvorbereitung von Ifosfamid und Deschlorethylmetaboliten in biologischem Material. 1. Mitteilung: Bestimmung in Plasma und Urin.

The cytostatic drug ifosfamide (IFF) and its main metabolites 2-dechloroethyl ifosfamide (2-D-IFF) and 3-dechloroethyl ifosfamide (3-D-IFF) were isolated from the plasma matrix with high recovery by solid phase extraction using Bakerbond C18-cartridges. A further cleaning of the extracts is not necessary. An effective separation of IFF and metabolites from interfering compounds present in urine samples prior gc was performed with Extrelut-1 and dichloromethane/isopropanol (95:5, v/v). The described assays may be used for pharmacokinetic studies as well as drug monitoring in the clinical laboratory.

Enantioselective determination of dimethindene in urine after oral administration of racemic dimethindene.

A sensitive high-performance liquid chromatographic determination of dimethindene and its metabolite N-demethyldimethindene in urine has been developed. The quantitative analysis was followed by determination of the enantiomeric ratio of dimethindene on an alpha 1-AGP column (EnantioPac). The urinary data for nine volunteers after oral administration of racemic dimethindene are presented. The isolation, identification and synthesis of the metabolite N-demethyldimethindene are reported.