AIM: Nifedipine and atenolol are the representative drugs for calcium antagonists and β-blockers, their combination use is the highly acclaimed anti-hypertension programs in clinical application. In order to assess t...AIM: Nifedipine and atenolol are the representative drugs for calcium antagonists and β-blockers, their combination use is the highly acclaimed anti-hypertension programs in clinical application. In order to assess the interaction of the two drugs, the bioequivalence and pharmacokinetics were investigated in a double layer tablet of compound formulation containing a sustained-release(SR) Nifedipine plus an immediate-release(IR) atenolol, compared with atenolol-IR tablet and Nifedipine-IR tablet individually in healthy Chinese subjects. METHODS: There were two stage tests: single-dose and multi-dose. In single-dose test, two random cross-over studies were performed in 20 young subjects who were given as monotherapy, a compound tablet (tested-drug, containing Nifedipine-SR 10 mg and atenolol-IR 25 mg) or two individual tablets (control-drug, a single Nifedipine-IR 10mg and a single atenolol-IR 25 mg) followed by a 12-hour-fast. In multi-dose test, two cross-over studies were performed in another 18 young subjects who were continuously treated for 7-days by two compound tablets once daily or two individual tablets (a single Nifedipine-IR 10 mg and a single atenolol-IR 25 mg) twice daily. The blood samples were collected at different time points before and after drug administration. Plasma drug concentrations were assessed by determining atenolol and Nifedipine with a validated HPLC or GC method. Safety and tolerance were evaluated by monitoring adverse events and laboratory parameters. RESULTS: No serious adverse events occurred in all subjects. There were no significant differences in pharmacokinetic parameters between atenolol in compound tablet and atenolol in single tablet. Cssmax, Cav and DF of Nifedipine sustained-release formulation were significantly decreased (90% CI, P<0.05), and tmax was significant extended (90% CI, P<0.05), compared with those of Nifedipine immediate-release tablet formulation in multi-dose studies. In single-dose treatment, the bioavailability of atenolol and nifidipine was 100%±14% and 124%±22%, individually. In multi-dose treatment, the bioavailability of atenolol and nifidipine was 85%±10% and 87%±16%, individually. CONCLUSION: Bioequivalence is equal in comparison between the fixed compound tablet and the individual tablets. The fixed compound tablet consistently provides fairly constant and effective atenolol concentrations. Nifedipine in the test drug is of sustained-release characters.展开更多
文摘AIM: Nifedipine and atenolol are the representative drugs for calcium antagonists and β-blockers, their combination use is the highly acclaimed anti-hypertension programs in clinical application. In order to assess the interaction of the two drugs, the bioequivalence and pharmacokinetics were investigated in a double layer tablet of compound formulation containing a sustained-release(SR) Nifedipine plus an immediate-release(IR) atenolol, compared with atenolol-IR tablet and Nifedipine-IR tablet individually in healthy Chinese subjects. METHODS: There were two stage tests: single-dose and multi-dose. In single-dose test, two random cross-over studies were performed in 20 young subjects who were given as monotherapy, a compound tablet (tested-drug, containing Nifedipine-SR 10 mg and atenolol-IR 25 mg) or two individual tablets (control-drug, a single Nifedipine-IR 10mg and a single atenolol-IR 25 mg) followed by a 12-hour-fast. In multi-dose test, two cross-over studies were performed in another 18 young subjects who were continuously treated for 7-days by two compound tablets once daily or two individual tablets (a single Nifedipine-IR 10 mg and a single atenolol-IR 25 mg) twice daily. The blood samples were collected at different time points before and after drug administration. Plasma drug concentrations were assessed by determining atenolol and Nifedipine with a validated HPLC or GC method. Safety and tolerance were evaluated by monitoring adverse events and laboratory parameters. RESULTS: No serious adverse events occurred in all subjects. There were no significant differences in pharmacokinetic parameters between atenolol in compound tablet and atenolol in single tablet. Cssmax, Cav and DF of Nifedipine sustained-release formulation were significantly decreased (90% CI, P<0.05), and tmax was significant extended (90% CI, P<0.05), compared with those of Nifedipine immediate-release tablet formulation in multi-dose studies. In single-dose treatment, the bioavailability of atenolol and nifidipine was 100%±14% and 124%±22%, individually. In multi-dose treatment, the bioavailability of atenolol and nifidipine was 85%±10% and 87%±16%, individually. CONCLUSION: Bioequivalence is equal in comparison between the fixed compound tablet and the individual tablets. The fixed compound tablet consistently provides fairly constant and effective atenolol concentrations. Nifedipine in the test drug is of sustained-release characters.
