Oruç E Elçin, Unsal Oya, Balkan Ayla, Ozkanli Fügen, Gören M Zafer, Terzioğlu Berna, Rollas Sevim
Marmara University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Istanbul, Turkey.
Eur J Drug Metab Pharmacokinet. 2006 Jan-Mar;31(1):21-5. doi: 10.1007/BF03190638.
The purpose of the study was to investigate the in vivo metabolic pathway of 3-oxo-5-benzylidene-6-methyl-(4H)-2-(benzoylmethyl)pyridazine (substrate) in rats. Firstly its potential metabolites, i.e. N-dealkylation, ring scission of pyridazine and aromatic hydroxylation products, were synthesized and then the substrate was given orally (100 mg/kg) to male or female Wistar rats at a dose of 100 mg/kg to body weight. Blood samples were collected at 0, 1, 2, 4, 6 and 8 hours after administration of substrate and blood was centrifuged to obtain serum. The substrate and its potential metabolites were separated using a gradient HPLC method on a reverse phase system. This study revealed that 3-oxo-5-benzylidene-6-methyl-(4H)-2-(benzoylmethyl)pyridazine was not metabolized to the proposed metabolites and was present unchanged in the serum.
该研究的目的是调查3-氧代-5-亚苄基-6-甲基-(4H)-2-(苯甲酰甲基)哒嗪（底物）在大鼠体内的代谢途径。首先，合成了其潜在代谢产物，即N-脱烷基化产物、哒嗪环断裂产物和芳香族羟基化产物，然后以100 mg/kg体重的剂量给雄性或雌性Wistar大鼠口服该底物。在给予底物后0、1、2、4、6和8小时采集血样，将血液离心以获得血清。使用反相系统的梯度高效液相色谱法分离底物及其潜在代谢产物。该研究表明，3-氧代-5-亚苄基-6-甲基-(4H)-2-(苯甲酰甲基)哒嗪未代谢为推测的代谢产物，而是以原形存在于血清中。
