Pharmacokinetics And Toxicokinetics Of M-nisoldipine In Beagle Dogs And Rhesus Monkeys

M-nisoldipine [3-isobutyl-5-methyl 1, 4 -dehydro-2,6 -dimethyl-4-(3- nitrophenyl ) -pyridine-3, 5-dicarboxylate, m-Nis ], an isomer of nisoldipine, is a new drug synthesized by Pharmacy College of Hebei Medical University, School of Pharmacy. By doing structure modification, the light stability of m-nisoldipine improved significantly compared to nisoldipine. Pharmacodynamics studies indicate that the pharmacological actions of m-nisoldipine are similar to nisoldipine. M-nisoldipine has a high selectivity to blood vessels, a powerful inhibitive effect to arterial contraction, a long term hypotension effect and a weak negative inotropic action to cardiac muscles, suggesting that m-nisoldipine is more efficient than nisoldipine and it has a prospect to become an ideal anti-hypertension medicine. Currently, the only pharmacokinetic study of m-nisoldipine was on rats and rabbits. The information about pharmacokinetic study of m-nisoldipine was limited.In this study, we established HPLC methods to determine the plasma m-nisoldipine concentration in Beagle dogs and Rhesus monkeys, study the pharmacokinetics of m-nisoldipine in Beagle dogs and Rhesus monkeys after intravenous administration, and investigate the toxicokinetics of m-nisoldipine in Beagle dogs after oral administration at high doses.PART ONE Study on the pharmacokinetics of m-nisoldipine in Rhesus monkeys after intravenous administrationOBJECTIVE: To establish a HPLC method for the determination of plasma concentration of m-nisoldipine in Rhesus monkeys, and to study the pharmacokinetics of m-nisoldipine after intravenous administration in Rhesus monkeys.METHODS: (1) Medication and plasma samples collection: Fifteen...