Chronopharmacokinetics of Amlodipine in Rats / 中国药学杂志

ABSTRACT

OBJECTIVE: To study the influence of circadian dosing time on pharmacokinetics of amlodipine in rats and to assess possible pharmacokinetic interactions. METHODS: Twelve male SD rats were divided into two groups, and a single dose of amlodipine (1 mgkg-1) were given intragastrically at either 8 00 or 20 00, respectively. Plasma samples were collected at 0, 0.33, 0.67, 1, 2, 4, 8, 12 and 24 h after drug administration. A HPLC-MS-MS detection method were developed to determine amlodipine concentrations in plasma. RESULTS: Absorption of amlodipine in rat was very slowly with MRT0-t about 12 h. Dosing time schedule influnced the pharmacokinetics of amlodipine dramatically and showed higher plasma drug levels (P<0.01), larger AUC (P<0.01) and lower CL/F (P<0.01) when dosing at 20 00 compared with that at 8 00 group. The difference of drug use between ρmax, AUC0-t and MRT0-t was statistically significant (P<0.05).The ρmax is three times as large as the morning medicine, AUC is four times as large as the drug in the morning. In the evening, MRT is extended for five hours longer than in the moring. CONCLUSION: The amlodipine plasma drug concentrations are lower, and CL/F, Vd/F are larger when dosing at 8 00 than those at 20 00.The administration of amlodipine at different times of a day shows a certain effect on the pharmacokinetics of amlodipine.