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Metabolic kinetics of MN9202 in Beagle dog liver microsomes / 药学学报
Acta Pharmaceutica Sinica ; (12): 1019-1023, 2005.
Article Dans Chinois | WPRIM | ID: wpr-253501
ABSTRACT
<p><b>AIM</b>To study the metabolic kinetics of MN9202 in Beagle dog liver microsome.</p><p><b>METHODS</b>Beagle dog liver microsomes were prepared by using ultracentrifuge method. After incubating 0.4 micromol x L(-1) MN9202 with 1 g x L(-1) microsomes for 30 min at 37 degrees C, the reaction was terminated by adding 0.5 mL alkalization. The RP-HPLC was used to determine the drug in the incubation mixture. The Michaelis-Menten parameters Km, and Vmax in Beagle dog liver microsomes were initially estimated by analyzing Lineweave-Brurk plot. Various selective CYP inhibitors were used to investigate their inhibitory effect on the metabolism of MN9202.</p><p><b>RESULTS</b>The Km, Vmax and CLint of MN9202 were (22.6 +/- 8.0) micromol x L(-1), (0.54 +/- 0.17) micromol x g(-1) x min(-1) and (0.0242 +/- 0.0009) L x g(-1) x min(-1), respectively. The metabolism of MN9202 was significantly inhibited by ketoconazole (Ket) and troleandomycin (Tro) in Beagle dog liver microsomes. Tranylcypromine (Tra) could inhibit the metabolism of drug as well. While other inhibitors showed little inhibitory effect on the metabolism of MN9202.</p><p><b>CONCLUSION</b>It was shown that CYP3A and CYP2C19 were involved in MN9202 metabolism. The inhibitors of human CYP3A and CYP2C19 may have potential interaction with MN9202, and this can reduce the metabolism rate and increase the toxicity of MN9202.</p>
Sujets)
Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Pharmacologie / Tranylcypromine / Microsomes du foie / Dihydropyridines / Pharmacocinétique / Aryl hydrocarbon hydroxylases / Inhibiteurs des canaux calciques / Troléandomycine / Cytochrome P-450 CYP2C19 / Inhibiteurs du cytochrome P-450 CYP3A Limites du sujet: Animaux langue: Chinois Texte intégral: Acta Pharmaceutica Sinica Année: 2005 Type: Article

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Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Pharmacologie / Tranylcypromine / Microsomes du foie / Dihydropyridines / Pharmacocinétique / Aryl hydrocarbon hydroxylases / Inhibiteurs des canaux calciques / Troléandomycine / Cytochrome P-450 CYP2C19 / Inhibiteurs du cytochrome P-450 CYP3A Limites du sujet: Animaux langue: Chinois Texte intégral: Acta Pharmaceutica Sinica Année: 2005 Type: Article