Metabolism of minaprine in human and animal hepatocytes and liver microsomes--prediction of metabolism in vivo.
1. The metabolism of minaprine and its major metabolite p-hydroxyminaprine were studied using hepatocytes and liver microsomes from different species. Metabolism of this drug in vitro was then compared with in vivo data already published. 2. Our results showed that the major metabolic route (4-hydroxylation of the aromatic ring) is the same in the two experimental systems. Other in vivo biotransformation pathways (i.e. N-oxidation, reductive ring cleavage, N-dealkylation, oxidation) were also confirmed in hepatocytes. 3. Similar inter-species variability was observed both in vitro and in vivo. The present study has led to the same conclusion as previous in vivo metabolic investigations, namely, that metabolism in the dog quantitatively differs from that observed in other animal species. 4. These results clearly demonstrate that in vitro models (i.e. isolated hepatocytes and liver microsomes) are powerful tools in predicting the metabolic pathways of a drug in man and animal species.
Lacarelle
B
B
INSERM U 278, Laboratoire de Toxicocinétique et Pharmacocinétique, Faculté de Pharmacie, Marseille, France.
Marre
F
F
Durand
A
A
Davi
H
H
Rahmani
R
R
D000327:Adsorption; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004285:Dogs; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D010215:Papio; D011724:Pyridazines / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D011724:Pyridazines; C006149:minaprine