Bioequivalence and pharmacokinetics of a compound sustained-release formulation of Nifedipine plus atenolol in healthy subjects

AIM： Nifedipine and atenolol are the representative drugs for calcium antagonists and 13-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.[第一段]

Bioequivalence and pharmacokinetics of a compound sustained-release formulation of Nifedipine plus atenolol in healthy subjects