title: Comparative pharmacokinetics and amoebicidal activity of metronidazole and satranidazole in the golden hamster, Mesocricetus auratus.
abstract: The pharmacokinetic properties of metronidazole and satranidazole were studied in the golden hamster (Mesocricetus auratus), at a dose of 80 mg/kg po. Blood and liver samples were collected at frequent time intervals and assayed for metronidazole and satranidazole by HPLC. Satranidazole exhibited significantly higher plasma concentrations than metronidazole at 1 and 2 h post-dose, but the comparative Cmax values were not significantly different. The satranidazole plasma elimination half-life of 1.01 h was significantly shorter than the corresponding metronidazole half-life of 3.62 h. The comparative liver pharmacokinetic parameters Cmax, Tmax and T1/2 did not differ significantly. Satranidazole however exhibited significantly higher liver concentrations at 1 h post-dose and Cmax and AUC0-infinity values were approximately 35% higher. The in-vivo amoebicidal activity of both compounds was evaluated in the acute hamster hepatic model of amoebiasis. Both metronidazole and satranidazole were administered as single graded doses po, and their dose-response profiles were characterized. Satranidazole demonstrated significantly greater amoebicidal activity than metronidazole with an ED50 value of 19.5 mg/kg, compared to an ED50 value of 45 mg/kg for metronidazole. These data suggest that higher plasma and liver concentrations of satranidazole and greater intrinsic potency probably contribute to superior amoebicidal activity in the hamster model of hepatic infection.
authors.affiliation: Research Division, Boots Pharmaceuticals Limited, Bombay, India.
authors.forename: A
authors.initials: A
authors.lastname: Pargal
authors.forename: C
authors.initials: C
authors.lastname: Rao
authors.forename: K K
authors.initials: KK
authors.lastname: Bhopale
authors.forename: K S
authors.initials: KS
authors.lastname: Pradhan
authors.forename: K B
authors.initials: KB
authors.lastname: Masani
authors.forename: C L
authors.initials: CL
authors.lastname: Kaul
mesh_terms: D000284:Administration, Oral; D000563:Amebicides / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D005260:Female; D006207:Half-Life; D008099:Liver / Q000378:metabolism / Q000469:parasitology; D008101:Liver Abscess, Amebic / Q000188:drug therapy* / Q000469:parasitology; D008647:Mesocricetus; D008795:Metronidazole / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D009593:Nitroimidazoles / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D000563:Amebicides; D009593:Nitroimidazoles; D008795:Metronidazole; C034473:satranidazole