Gas chromatographic-mass spectrometric assessment of the pharmacokinetics of amineptine and its main metabolite in volunteers with liver impairment.
A pharmacokinetic study of amineptine (Survector) and its C5 metabolite, resulting from a beta-oxidation of the heptanoic acid side-chain, was undertaken with ten human volunteers, who received a single 100-mg tablet of amineptine orally. They were affected with liver impairment in order to determine if this situation would alter greatly the pharmacokinetic parameters. The internal standard was the octanoic acid homologue. Analyses were carried out by gas chromatography (GC) and GC-mass spectrometry using TMS ester derivatives. Plasma samples were extracted using a C18 reversed-phase cartridge at pH 4.0. Mass fragmentographic measurements on the plasma samples were performed on the m/z ions (M + H)+ and (base peak)+ using ammonia chemical ionization. The global evaluation of precision was good and the coherence between the two modes of measurements, (base peak)+ and (M + H)+ ions, gave a regression factor r close to unity. For amineptine the total body clearance and mean residence time were accurate and precise with eight volunteers, but only four volunteers showed such coherent data for the slope of the elimination curve, beta, and half-life. However, the beta value, half-life and mean residence time of the C5 metabolite were accurate and precise with seven, eight and ten volunteers, respectively. It is concluded that the drug was still detoxified at normal levels.
Tsaconas
C
C
Laboratoire de Biochimie Médicale, Faculté de Médecine, Dijon, France.
Padieu
P
P
d'Athis
P
P
Mocaer
E
E
Bromet
N
N
D000328:Adult; D000368:Aged; D003986:Dibenzocycloheptenes / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D007202:Indicators and Reagents; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011619:Psychotropic Drugs / Q000097:blood / Q000493:pharmacokinetics*
D003986:Dibenzocycloheptenes; D007202:Indicators and Reagents; D011619:Psychotropic Drugs; C011597:amineptin